To assess the anti-inflammatory function and possible molecular mechanism of rice bran polysaccharide (RBP), DSS-induced colitis model was used in ICR mice. Pathological changes and gene expression were analyzed by histopathological analysis, RT-qPCR and Western blotting among of different experiment groups. The results showed that 500 mg/kg/day RBP could significantly improve the health status of mice and reduced colonic inflammation. RBP reduced the disease active index (DAI) score of DSS-induced mice and alleviated the damage of pathological tissue, with the improvement of the inflammation-related biochemical indicators. qRT-PCR analysis showed that RBP could decrease the mRNA expression level of inflammatory factors, including TNFα, IL-1β, Cox-2 and iNOS in colon tissues. Western blotting analysis further confirmed the efficacy of RBP inhibiting the expression level of inflammatory factor protein. Moreover, RBP could also inhibit MAPK signaling pathway. The results suggested that RBP had anti-inflammatory effect, and its molecular mechanism might be related to down-regulating the expression of inflammatory factors via inhibiting MAPK signaling pathway.