Abstract: Objective To investigate the relationship between the levels of serum homocysteine（Hcy）,high-sensitivity C-reactive protein（hs-CRP） and interleukin-8（IL-8） and the efficacy of type 2 diabetes mellitus（T2DM） patients with depression. Methods A total of 110 T2DM patients with depression who were diagnosed in Cangzhou Central Hospital from December 2015 to December 2017 were enrolled.All patients were administrated with citalopram and risperidone for hypoglycemic and antidepressant treatment.According to self-rating depression scale（SDS）scores,the patients were divided into two groups（n=55）:an excellent group and a general group.The two groups were compared for general information,the degree of psychological disorder and blood glucose changes before and after treatment.The levels of serum Hcy were measured by the circulating enzymatic method.The levels of hs-CRP were determined by immunoturbidimetry.The levels of serum IL-8 were detected by ELISA.Furthermore,the Pearson product moment correlation coefficient was used to analyze the correlation between patient efficacy and the levels of the three serum markers. Results After treatment,both groups showed remarkable decreases in SDS and HAMD scores compared with those before treatment（P＜0.05）,where marked reduced SDS and HAMD scores were found in the excellent group in comparison with those in the general group（P＜0.05）.The levels of blood glucose were decreased in each group after treatment（P＜0.05）,but no statistical difference was found between the two groups（P＞0.05）.After treatment,the levels of each marker in the two groups were significantly lower than those before treatment,where marked decreases were found in the excellent group compared with the general group（P＜0.05）.There were positive correlations between the three serum markers and SDS scores in the treatment group（P＜0.05）,where Hcy has the strongest correlation with depression change（P＜0.05）.Conclusions After treatment,the levels of serum Hcy,hs-CRP and IL-8 were positively correlated with the degree of depression in T2DM patients with depression,which may provide evidence for improving the efficacy of T2DM patients with depression.