Abstract: Objective: To explore the effect of Astragali radix polysaccharide on ulcerative colitis and its mechanism. Methods: Fifty SPF male mice were randomly divided into the normal control group, the model group, the high and low concentration APS group, and the positive group. The mouse model of acute ulcerative colitis was established with 5% dextran sulfate sodium salt. After the successful model establishment, the normal control and the model group were free to drink distilled water, the high and low concentration APS groups were free to drink 0.7 and 0.35 mg·mL⁻¹ APS aqueous solution respectively, and the positive group was free to drink 1 μg·mL⁻¹ dexamethasone aqueous solution for 7 consecutive days. Assessing disease activity index (DAI) of mice in each group, observing colonic pathological sections by HE, and detecting superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, nitric oxide synthase (NOS) activity, malondialdehyde (MDA) content and nitric oxide (NO) levels in tissues, and then detecting interleukin-6 (IL-6), leukocyte-mediated Interleukin-1β (IL-1β), D-lactic acid (D-LA), diamine oxidase (DAO), and tumor necrosis factor-α (TNF-α) content in serum by ELISA method. Results: Compared with the DSS group, the high concentration APS group significantly (P<0.05) reduced the DAI score of mouse colitis, reduced the area of colon tissue ulcers and inflammatory cell infiltration, and restored the length of the colon, and the concentrations of IL-6, IL-1β, TNF-α and the levels of D-LA and DAO in the serum were significantly decreased. The activities of MPO, NOS, MDA and NO in colon tissue were obviously (P<0.05) decreased, while the activities of SOD were significantly (P<0.05) increased. Conclusion: The high concentration APS group had a notable effect on mice with ulcerative colitis, its effect was related to antioxidation, improvement of intestinal mucosal barrier function, and reduction of the release of inflammatory factors.