Abstract: Objective To analyze the role BDNF plays in depressive patients with diabetes and to explore whether BDNF is correlative risk factors in type 2 diabetes and depression.Methods A prospective case-control study was done in which 45 depressive patients with 2 type diabetes (DDM group) and 41 without diabetes(NDDM) were in cluded. The health control group consisted of 45 healthy people. Demographic data, psychological scale, sugar metabolism, diabetes complications, medical indicators and serum brain-derived neurotrophic factor levels before and after treatment were collected and Logistic regression models constructed.Results BDNF in DDM Group and NDDM groups was of statistical difference before and after treatment(P<0.001). After treatment BDNF levels were higher than those before treatment levels, indicating that after the adoption of antidepressant treatment, serum BDNF levels improved significantly; for patients with depression, BDNF levels were found to be protective factors for depression, OR=0.782,95% CI (0.702-0.872), and with higher levels of BDNF, the risk of suffering from depression became smaller; with age, FPG and BDNF levels in depression with type 2 diabetes, age and FPG were risk factors for the disease, while serum BDNF was a protective factor, OR=0.835,95% CI (0.736-0.948).Conclusion BDNF proves to be one of the important biological factors for type 2 diabetes and depression co-morbidity and its higher levels are protective factors for the disease. In this study, serum BDNF has been investigated to obtain a basis for reference in this regard.