Globally, the number of persons with type 2 diabetes (T2DM) makes up 95% of the total number of diseased. According to the data of the International Diabetes Federation, the real number of diseased is far higher than the number of registered ones, because in 30-80% of cases, persons with T2DM they have no diagnosis and do not know about their disease. T2DM is considered to be one of the most demanding chronic diseases, both physically and emotionally, and living with diabetes is a challenge for majority of diseased. Despite the fact that self-management of diabetes is considered as equally important as a treatment by a doctor and ensures that a person makes 90-95% of decision about his disease independently, high behavioral requirements (regimens of nutrition, body weight management, physical activity and medication adherence) may, at certain periods of a life, become too hard and lead to symptoms of depression and diabetes related distress, a psychological reaction to the threat of diabetes, or a conditions in which a person with diabetes thinks that the resources at their disposal, are insufficient to manage the threat posed by the disease. Psychosocial characteristics of persons with T2DM (cognitive perception of the disease, coping strategies, self-confidence and motivation) mediate the relationship between behavioral determinants of diabetes self-management and these psychological states. As metabolic control is goal of self-management of diabetes, symptoms of depression and diabetes-related distress can directly, but also indirectly, result in poorer metabolic control and progression of complications with a negative impact on quality of life, whereby a decline in quality of life leads to the onset or worsening existing depression and diabetes-related distress. Goal: to examine the relationship between behavioral determinants of diabetes self-management, mediating psychosocial characteristics and psychological states (depression and diabetes-related distress) and their predictive impact on metabolic control and quality of life of persons with T2DM. Methods: The study was conducted as a descriptive analytical cross-sectional study that included 324 subjects diagnosed with T2DM, set in accordance with the American Diabetes Association (ADA) criteria, controlled and treated at the Diabetes Dispensary of the Health Center in Zajecar. Respondents were determined by a random sampling method. This reduced selection bias and provided a statistically reliable estimate of the large number of variables included in the study. The following laboratory parameters were taken from medical documentation of subjects who came for control examination and considered in relation to ADA criteria for good metabolic control: glycosylated hemoglobin (HbA1c), serum triglycerides, low-density lipoproteins (LDL-C) and High-density lipoproteins (HDL-C). The subjects’ blood pressure was measured at two times and the mean value was calculated. Anthropometric measurements (body mass and body height) were performed, body mass index were calculated and interpreted in accordance with ADA guidelines Sets of questionnaires were used as research instruments, which contained the following elements: General questionnaire (made for the needs of this research), Questionnaire on Attitudes towards Medication Adherence, Questionnaire on Perception of Adherence to Dietary Recommendations, subscales of the Personal Diabetes Questionnaire (assessment of physical activity and motivation for changes in self-management of diabetes), Diabetes Self-Confidence Scale, Depression Symptom Assessment Questionnaire (PHQ-9), Diabetes Distress Scale and Short Clinical Questionnaire on Quality of Life with Diabetes. Statistical data processing was performed using the statistical program IBM SPSS Statistics 21.0. The data are presented in tables and graphs. Statistical significance was determined at the level of 95% (p < 0.05). Results: Symptoms of depression were present in 60,8% of respondents in the sample (10.2% had symptoms of severe depression), while 35.2% of respondents had clinically significant diabetes-related distress. Predictive values in relation to depressive symptoms was shown by female gender, the presence of diabetes complications, and inadequate coping strategies, while low self-confidence and inadequate coping strategies were predictors of diabetes-related distress. In the study sample 47.8% of respondents had negative attitudes toward medication adherence, 65.1% of them rated their compliance with dietary recommendations as unsatisfactory, while 55.9% of respondents rated their physical activity as unsatisfactory. Predictive value in relation to attitudes towards medication adherence was shown by: poor glycemic control, insulin therapy that respondents perceived as a burden, unsatisfactory physical activity, non-adherence toward dietary recommendations and inadequate coping strategies. Predictive value in relation to unsatisfactory compliance with dietary recommendations was shown by: obesity, low self-confidence and lack of motivation to compliance dietary recommendations, while predictive value in relation to unsatisfactory level of physical activity was shown by: presence of complications, lack of motivation to control body mass and low self-confidence. Clinically significant diabetes-related distress was a more significant predictor of all behavioral determinants of diabetes self-management, relative do depressive symptoms. Behavioral determinants of self management of diabetes are statistically negatively associated with each of the parameters of metabolic conrtol individually. Diabetes-related distress is statistically significantly positively associated with HbA1c and blood pressure values, while respondents with symptoms of depression have poorer glycemic control and lipid status outside the reference values. Poor metabolic control, unfulfilled all three goals of metabolic control (glycemic control, lipid status and blood pressure) according to ADA criteria, have 78.4% of respondents. Predictive value in relation to poor metabolic control was shown by: obesity, insulin therapy which respondents perceive as a burden, non adherence toward dietary recommendations and unsatisfactory physical activity. Unsatisfactory quality of life is expressed by 62.0% of respondents. Predictive value in relation to unsatisfactory quality of life was shown by: the presence of complications, low self-confidence, non-adherence toward dietary recommendations, unsatisfactory physical activity, symptoms of depression and clinically significant diabetes-related distress. Conclusion: The synthesis of data and information obtained by this research can be crucial in the implementation of public health programs aimed at persons with T2DM. The results obtained by this study indicate that the available therapeutic modalities are less likely to be effective in persons who have difficulty adhering to the behavioral determinants of self-management of their disease. Most determinants of diabetes self-management (adequate dietary regimes, body mass control and physical activity) are often beyond the reach and influence of physicians treating persons with T2DM and are likely to be much more susceptible to public health interventions. Taking into account data on a number factors influencing the metabolic control and quality of life of persons with T2DM, obtained as a results of this and similar research, can be the basis for involving individuals in structured public health programs on healthy lifestyles. In any case, multidisciplinary approach must be a priority in future interventions aimed at improving the treatment outcomes of persons with T2DM. This would create the possibility of synergy of structured lifestyle and pharmacotherapeutic interventions in accordance with ADA recommendations about individualized and comprehensive approach to persons with T2DM. By introducing in routine work with T2DM patients questionnaires applied in this research as well as short clinical interviews on how they experience their disease and how to deal with the problems associated with it, would allow physicians a much more individualized and comprehensive approach to their patients. This follows from the results of this study which indicate the connection and influences of the patient’s personality (psychosocial and affective properties) on the behavioral determinants of diabetes self-management, and thus indirectly and directly on the metabolic control and quality of life of persons with T2DM.