Objective To investigate the efficacy of sertraline hydrochloride combined with mesalazine in the treatment of patients with ulcerative colitis complicated with depression .Methods From March 2014 to March 2015 ,eighty patients with mild active ulcerative colitis ,self‐rating depression scale (SDS) score between > 53 and 70 points ,were enrolled .Eighty patients were divided into sertraline hydrochloride combined with mesalazine group and mesalazine group (control group) ,40 patients in each group .SDS questionnaire and gastrointestinal endoscopy were applied at the beginning of the study and 12 weeks after treatment to evaluate the efficacy .Chi square test or t test was performed for statistical analysis .Results After 12 weeks treatment ,the efficacy of mesalazine combined with sertraline group and mesalazine group was 75% (30/40) and 65% (26/40) , respectively ,and the difference was not statistically significant ( P > 0 .05 ) .Before the treatment ,ulcerative colitis activity index (UCAI) of mesalazine combined with sertraline group and mesalazine group was 13 .13 ± 4 .41 and 12 .41 ± 3 .96 , respectively ;12 weeks after treatment ,the UCAI of the two groups were 7 .29 ± 5 .78 and 8 .60 ± 4 .56 , respectively .The UCAI of both the two groups were lower than those before treatment , and the differences were statistically significant (t= 6 .106 7 and 5 .189 3 ,both P < 0 .01) .The difference was not statistically significant in UCAI between the two groups after treatment (P > 0 .05) .Before treatment ,SDS score of mesalazine combined with sertraline group and mesalazine group was 55 .98 ± 9 .61 and 56 .27 ± 8 .45 , respectively ;12 weeks after treatment ,SDS scores of the two groups were 49 .36 ± 4 .51 and 52 .81 ± 6 .11 ,respectively .Compared with those before treatment , after 12 weeks treatment , SDS scores of mesalazine combined with sertraline group and mesalazine group both decreased (t= 3 .944 0 ,P= 0 .000 2 ;t=2 .098 6 ,P= 0 .039 1) .After treatment ,SDS score of mesalazine combined with sertraline group was lower than that of mesalazine group (t = 2 .873 2 , P = 0 .005 2) .Conclusion Routine ulcerative colitis treatment combined with sertraline hydrochloride in ulcerative colitis can significantly improve depression of ulcerative colitis patients and improve the quality of patients′ life .