Abstract: The study aims to explore the effects of N-p-chlorobenzenesulfonyl-4-amino salicylic acid on the dextran sodium sulfate (DSS)-induced ulcerative colitis in mouse. A total of 60 BALB/c mice were randomly divided into 6 groups (n=10):control group, DSS model group, 5-amino salicylic acid (5-ASA) group, and administration groups (N-p-chlorobenzenesulfonyl-4-aminosalicylic acid) 10, 20, 40 mg·kg^-1. Model group were induced by drinking 4% (w/v) DSS solution for 7 days and normal water for the next 3 days. The positive group and drug group mouse were given 5-ASA (40 mg·kg^-1) and N-p-chlorobenzene sulfonyl-4-amino salicylic acid (10, 20, 40 mg·kg^-1) by gavage respectively. During the experiment, changes in body weight, bloody stool, fecal character and mental status were observed daily. Damage and repair of the colon mucosa and the pathological changes of important organs were observed by hematoxylin and eosin (HE) staining. Expression of inflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), macrophage inflammatory protein 2 (MIP-2), myeloperoxidase (MPO) in serum were detected by ELISA. The results showed that bloody stools and diarrhea emerged on the 4^th day after model establishment in model mice. The number of bloody mice rose to ten, and blood and diarrhea began to appear in the administration group on the 7^th day. Mental status was poor and body weight decreased significantly in model group since the 4^th day, and the situation was improved in the administration group and 5-ASA group. Colons in the administration groups (10, 20, 40 mg·kg^-1) were longer than those in the DSS model group. In the DSS model group, the colonic mucosa and submucosa of mice exhibited severe inflammatory cell infiltration, various degrees of necrosis, proliferation. In the middle dose group (20 mg·kg^-1), the situation has improved slightly and the colonic mucosa showed mildly chronic inflammation and a small amount of inflammatory cells infiltration. The high dose group (40 mg·kg^-1) showed normal colon mucosal, relatively complete epithelial structure and few inflammatory cell infiltration. The levels of IL-1β, IL-6, TNF-α, MIP-2 and MPO in the serum of mice were lower in the administration group (40 mg·kg^-1) than in model group. Therefore, N-p-chlorobenzenesulfonyl-4-amino salicylic acid might be a feasible treatment for DSS-induced UC.