Objective To investigate the effect of mesalazine on the expression of TNF-α, IL-6, IL-17 and intestinal barrier function in patients with ulcerative colitis. Methods 76 patients with UC from January 2015 to April 2016 in The Fifth Central Hospital of Tianjin were collected and randomly divided into control group and observation group with 38 cases in each group. After admission were given maintenance of water and electrolyte, basic acid-base balance and nutritional support treatment, and the control group were treated with conventional drug sulfasalazine (SASP) treatment, two tablets each time, four times once day, four weeks for each course, the observation group was treated with mesalazine, four tablets each time, three times once day, four weeks each course of treatment. The levels of TNF-α, IL-6, IL-17, L/M and Baron endoscopic scores in the two groups were observed after two courses of treatment. The efficacy and side effects of the two groups were compared. Results No dropout or dropout cases in this study, two groups after the treatment of TNF-α, IL-6, IL-17, L/M, Baron scores were significantly decreased (P<0.05), but the observation group after treatment the above indexes were all significantly lower than the control group (P<0.05), the total effective rate of the observation group was 89.47%(34/38) higher than that of the control group 71.05%(21/38), the adverse reaction rate of 13.16% (5/38) was lower than that in the control group 34.21% (13/38), the differences were statistically significant(P<0.05). Conclusion Compared with conventional drug SASP, the effect of on the expression of TNF-α, IL-6 and IL-17 in serum of patients with UC and the improvement of intestinal barrier function can be effectively suppressed, which has the advantages of clinical efficacy and low adverse reaction rate.