To investigate the different doses of Changyuning granules on the expression of IL-1β,TNF-α and IL-4 in mice with ulcerative colitis (UC) and observe its immune mechanism against UC. Methods:Forty-eight male wistar rats were randomly divided into six groups:control group,model group, high-dose group,medium-dose group,low-dose group of Changyuning granules, mesalazine group.The UC models were established by TNBS/ethanol composite enema, disease activity index (DAI),colon macroscopic damage index (CMDI) and tissue damage index (TDI) were assessed.Serum IL-1β,TNF-α and IL-4 were detected by ELISA. Results:Injection of 5% TNBS 50 mg/kg+50% ethanol 0.25 mL for one week could successfully lead to ulcerative colitis (UC) in rats and Changyuning granules can resist UC induced rats.Compared with the model group,the DAI,CMDI and TDI scores of the high-dose group and the middle-dose group of Changyuning granules were all reduced,the expression of IL-1β, TNF-α was down-regulated and the expression of IL-4 was up-regulated. Conclusion:Changyuning granules have significant resistance to ulcerative colitis (UC).The mechanism may be related to reducing the expression of the TNF-α as well as IL-1β and increasing the expression of the IL-4.