Abstract： AIM To compare the curative effect of three different routes of mesalazine administration in the treatment of patients with mild to moderate ulcerative colitis (UC).METHODS A total of 227 mild to moderate UC cases were recruited at the Sixth Affiliated Hospital of Sun Yat-sen University from July 2012 to May 2015.Oral,topical,or combined route of administration of mesalazine was adopted.At 30 d and 1 year after treatment,clinical efficacy was compared among different groups,and related epidemiological risk factors were retrospectively identified.RESULTS For all the included UC patients,the total effective rate at 30 d was 76.00％ for the oral medication group,79.31％ for the local group,and 93.64％ for the combined group,and there was a significant difference in the total effective rate between the oral and combined groups (x2 =8.662,P =0.003) and between the local and combinetl groups (x2 =6.618,P =0.010),but not between the oral and local groups.At 1 year,the effective rates of the three groups were 62.50％,73.08％,and 91.84％,respectively.For each administration route,there was no significant difference in the effective rate between longterm and short-term observation.However,the longterm complete remission rate in the single-route groups showed an obviously decreasing trend (oral 28％ vs 12.50％,local 34.48％ vs 15.38％),while the curative effect in the combined group was stable (51.02％ vs 50.87％).Logistic regression analysis showed that administration route was an independent risk factor affecting the effect of mesalazine,while gender,age,smoking,BMI,disease duration,and lesion degree/range were not.CONCLUSION Mesalazine is an effective drug to treat mild to moderate UC.Combined oral/topical usage has higher efficacy than each of the two separate applications.