Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (SI), glucose effectiveness (SG), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters of SI, SG, and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77 to 1.30 pg/ml; P=.001) after antidepressant therapy. However, the concentrations of CRP, TNF-α, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.