Abstract: Objective To observe the clinical efficacy of Omega-3 polyunsaturated fatty acids (omega-3PUFAs) in the treatment of ulcerative colitis (UC) and its influence on peripheral blood Th17/Treg cell balance and the levels of cytokines IL-10 and IL-17. Methods A prospective randomized controlled study was conducted. Fifty patients with UC were enrolled from Lishui Central Hospital in Zhejiang province from January, 2014 to December, 2016. The time and place of the study were added. The patients were divided into 2 groups by random number table. Twenty-five cases in Control group, mesalazine 1 g 4 times a day orally; 25 cases in Observation group, mesalazine 1 g 4 times a day orally and ω3-PUFAs 100 ml 1 times a day intravenous drip. Other nonspecific treatment measures were the same in the two groups, and the course of treatment was one weeks. The expressions of serum IL-10 and IL-17 were detected by ELISA, and the proportion of Treg cells and Th17 cells in peripheral blood was detected by flow cytometry. The clinical effective rates of the two groups were compared. The levels of serum IL-10 and IL-17, the ratio of Treg cells and Th17 cells in peripheral blood before and after the treatment were compared. Results There was no significant difference between the two groups in age, sex, course of disease and severity of the disease (P>0.05). The total effective rate of clinical symptom improvement in the observation group (88%) was obviously better than that of the control group (68%), the difference was statistically significant (P<0.05). Compared with the same group before treatment, the proportion of Treg cells and IL-10 levels in peripheral blood of both groups increased significantly, while the proportion of Th17 cells and the level of IL-17 were significantly decreased, the difference was statistically significant (P<0.05). Compared with Control group, the proportion of Treg cells and IL-10 levels in peripheral blood of the observation group increased more significantly, but the proportion of Th17 cells and the level of IL-17 decreased more significantly, the difference was statistically significant (P<0.05). Conclusion ω-3 PUFAs has good clinical efficacy in the treatment of UC, and its mechanism may be related to regulating the balance of Treg/Th17 and alleviating the inflammatory reaction of UC.