Objective To observe the effect of mussel adhesive protein(MAP) on the intestinal mucosa of rats with ulcerative colitis, and to explore potential mechanisms from the perspectives of adhesion and antioxidant actions. Methods A total of 32 specific pathogen-free grade SD rats were randomly divided into four groups: a normal group, model group, mesalazine group and MAP group (0. 6 mg / kg body weight), with eight rats in each group. The normal group was provided ordinary drinking water, whereas the other groups were given 5% dextran sodium sulfate (DSS) for 7 days to induce ulcerative colitis, and daily dosing was started during the 24 h after molding. The disease activity index (DAI) scores and body weights of the rats in each group were observed and recorded. After 7 days of DSS administration, samples were collected to determine the colorectal length and intestine:body weight ratio for each group, and the histology and gross morphology of the colorectal mucosa were examined. The adhesion and antioxidant effects of MAP on the intestinal mucosa of rats was investigated in vitro by nitro blue tetrazolium chloride (NBT) staining. Results Compared with the normal group, the model group showed significantly higher DAI scores (P< 0. 05) and a decreased body weight (P< 0. 05) from day 5 onwards, and shorter colorectal length and lower intestinal weight ratio (P< 0. 05), as well as higher colon mucosal damage index (CMDI) (P< 0. 05) and pathohistological (P< 0.05) scores. Congestion, edema, and ulceration were observed in the colorectal mucosa, as well as swelling and distortion of the colonic crypts and extensive infiltration of inflammatory cells in submucosal tissue. These findings showed that the ulcerative colitis model was successfully established in rats. Compared with the model group, the body weight and colorectal length of rats in the mesalazine and MAP groups were increased (P< 0. 05), whereas DAI scores, intestinal weight ratio, and CMDI and histopathological scores were decreased (P< 0. 05). In comparison with the mesalazine group, rats in the MAP group showed similar body weight growth trends and DAI scores, as well as similar levels of intestinal mucosal edema, congestion and inflammatory cell infiltration, indicating that MAP had potentially similar therapeutic effects to those of mesalazine in ulcerative colitis. The NBT staining produced blue histology in the rectal mucosa of rats, and the degree of blue staining increased with time. Conclusions Through adhesion and antioxidant effects on intestinal mucosa, MAP can significantly improve the symptoms of dilute stool, blood in stool and weight loss in rats with ulcerative colitis, and repair a damaged intestinal mucosal barrier. Additionally, MAP reduced the congestion and edema of rat rectal mucosa, as well as effectively reduced the infiltration of inflammatory cells, suggesting therapeutic potential for the treatment of ulcerative colitis by MAP.