Objective To investigate the changes of plasma monocyte chemoattractant protein-1 （MCP-1） and its relationship with body mass index（ BMI） and gender in patients with first-episode major depressive disorder（ fMDD）. Methods In this prospective case-control study， 47 first-episode depressive patients（ meeting the diagnostic criteria for major depressive disorder， fourth edition of the diagnostic and Statistical Manual of mental illness） were enrolled as the research subjects. 91 health individuals matched in age and sex were enrolled as the control group. The plasma level of MCP-1 was measured by MILLIPLEX MAP liquid chip system. The difference of MCP-1 levels was analyzed between fMDD patients and controls. In order to analyze the relationship between MCP-1 and BMI， gender， the participants were divided into underweight， normal， overweight and obese groups according to BMI. Results The plasma MCP-1 levels in fMDD patients were（ 197.61±60.73）ng/L， which was lower than that in the control group（ 222.29±65.49） ng/L P=0.035）. The level of plasma MCP-1 was positively correlated with BMI in both healthy controls（ r=0.360， P＜0.001） and fMDD patients（ r=0.435，P=0.003）. The MCP-1 level of fMDD patients with low and normal BMI ［（181.21±47.12）ng/L］ was significantly lower than that of controls with low and normal BMI［ （212.54±64.35）ng/L； t=2.481，P=0.015］. There was no statistical significance in the MCP-1 level difference between the two groups in overweight and obese participants（ P＞ 0.05）. The MCP-1 level of male participants in fMDD group ［（207.86±59.54）ng/L］ was lower than that in the control group［ （262.95±66.24）ng/L］， with statistical significance（ t=2.829，P=0.007）. There was no significant change in MCP-1 levels in female patients compared with the controls（ P=0.639）. Conclusions The results indicated the plasma MCP-1 levels were significantly reduced in the fMDD patients compared to controls， especially in male patients， and the decrease of MCP-1 level was related to the degree of obesity in fMDD patients， suggesting that the interaction between MCP-1 and obesity was closely related to depression.