OBJECTIVE: To explore the repairing effect and mechanism of Huazhuo jiedu yukui formula on the mucosal damage of rats with ulcerative colitis (UC). METHODS: 72 rats were randomly divided into blank group, model group, mesalamine group (positive control, 0.3 g/kg), Huazhuo jiedu yukui formula low-dose, medium-dose, high-dose groups (5, 10, 20 g/kg), 12 in each group. Except for blank group, other groups were induced UC model. After 4 d of modeling, rats in administration groups received related medicines, ig, blank group and model group received normal saline, ig, once a day, for 2 weeks. After administration, disease activity index (DAI) and mucosal damage index (CMDI) of rats were observed; IL-8, TNF-α contents in serum and cyclooxygenase 2 (COX-2) expression in colon tissue were detected. RESULTS: Compared with blank group, DAI and CMDI scores in model group were increased; IL-8, TNF-α contents in serum were increased; COX-2 expression in colon tissue was enhanced, with statistical significances (P<0.05). Compared with model group, DAI and CMDI scores in model group were decreased; IL-8, TNF-α contents in serum were reduced; COX-2 expression in colon tissue was weakened, with statistical significances (P<0.05). Compared with mesalamine group, the above-mentioned indicators in Huazhuo jiedu yukui formula medium-dose, high-dose groups changed more obviously (P<0.05), and effects of Huazhuo jiedu yukui formula showed significant dose-effect relationship. CONCLUSIONS: Huazhuo jiedu yukui formula can improve disease activity status of UC rats and reduce colon mucosal damage, and the effects of medium-dose and high-dose Huazhuo jiedu yukui formula were better than mesalamine, which may be related to reducing inflammatory reaction and inhibiting COX-2 expression in colon tissue.