Abstract: Objective To establish an animal model suitable for evaluating the efficacy of an anti-damp-heat (DH) ulcerative colitis compound in Chinese medicine and for new drug development, and to explore the difference and connection between ordinary ulcerative colitis (UC) and UC with DH syndrome. Methods Twenty-four SD rats were randomly divided into the blank control group, UC group and UC+DH group. Rats in the UC group were induced by 5% dextran sodium sulfate (DSS), and the UC+DH group was induced by “ high-fat and high-sugar diet + alcohol + hunger and satiety alternately + high temperature and humidity environment + 5% DSS” for 29 d. The general condition of rats was observed every day for the disease activity index(DAI) and Geboes colonic histopathological scores. Serum levels of ALP, ALT, AST, CHOL, GLU, HDL-C, LDL-C, LDH and TG, and colonic activity of GSH, MDA and MPO were detected. Serum cortisol and colon expression of HSPs, IL-10, MIP-1α, MIP-1β and TNF-α were detected by ELISA. Results The two models exhibited different degrees of intestinal inflammation, increased DAI and Geboes scores, and different degrees of damage to liver function. Compared with the UC group, pathological changes were more severe in the UC+DH group. In addition, serum levels of TG, LDL-C, ALP, ALT, AST, CHOL, cortisol, DAO, HSPs, MDA, MPO, MIP-1α, MIP-1β and TNF-α, and colonic levels of GSH and IL-10 were significantly increased in the UC+DH group, whereas the serum concentration of HDL-C was significantly decreased. Conclusions Intestinal mucosal injury and liver injury were found in both rat UC models. However, the hot and humid environment aggravated the degree of intestinal mucosal injury induced by DSS in UC rats, and its mechanism may be related to promoting inflammation, lipid peroxidation, and intestinal mucosal permeability.