Objective? To study the effect of Qingre Lishi Yichang Decoction on the colonic mucosal lesions and serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) in patients with ulcerative colitis. Methods A total of 82 patients with ulcerative colitis in the 924th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army from May 2018 to May 2019 were selected and divided into the control group and the test group according to the random number table method, each group with 41 cases. Patients in the control group were treated with Sulfasalazine, and patients in the test group were treated with Qingre Lishi Yichang Decoction on the basis of the treatment of the control group, 60 days were a course of treatment, and both groups were carried out for 2 courses. Compared the clinical efficacy of the two groups of patients after treatment, and the colonic mucosa Baron score, quality of life scale (SF-36) score and serum IL-6, TNF-α, CRP levels of patients before and after treatment, and the total incidence of adverse reactions during treatment. Results? After treatment, the total effective rate in the test group was 97.56%, which was significantly higher than 78.05% in the control group; after treatment, the colonic mucosal Baron score and serum IL-6, TNF-α, and CRP levels of the two groups were significantly lower than before treatment, and the test group was significantly lower than the control group, the scores of general health, mental health, physical pain, and social function of the two groups of patients were significantly higher than before treatment, and the test group was significantly higher than the control group (all P <0.05); comparison of the total incidence of adverse reactions of patients between the two groups during treatment,the difference were not statistically significant (P >0.05). Conclusion Qingre Lishi Yichang Decoction on the colonic mucosal lesions can effectively improve the pathological changes of the colonic mucosa and the quality of life of the patients, reduce the level of inflammatory factors in the patient's body, and improve the therapeutic effect, and the security is good.