〔Abstract〕 Objective To investigate the effect and mechanism of ARRB1 on Armillariella tabescens polysaccharides reversal of 5-fluorouracil(5-FU)-induced chemotherapeutic intestinal mucosal injury. Methods Twelve ARRB1 knockout(ARRB1-/-) and wild-type(WT) C57BL/6 mice were randomly divided into Control, Model and ATPS groups(200 mg/kg),respectively.5-FU(50 mg/kg) was injected intraperitoneally for 7 days to establish a model of chemotherapeutic intestinal mucosal injury.The histopathological damage of jejunum was evaluated by HE staining; the activity of serum superoxide dismutase(SOD) and diamine oxidase(DAO) was measured by kits; the expression of tight junction protein(TJ) markers ZO-1,Occludin, Claudin-1 and proliferation-associated protein Ki-67 was detected by immunohistochemistry.Crypt isolation and organoid culture were used to detect the growth status of small intestinal organoids. Results 5-FU chemotherapy reduced body weight, aggravated histopathological damage in small intestine, decreased SOD level, TJ protein and Ki-67 protein expression, increased serum DAO level, decreased spherical structure formation rate and organoid formation rate; compared with the model group, after ATPS treatment, WT mice recovered body weight, decreased pathological damage, increased serum SOD level, TJ protein and Ki-67 protein expression, DAO levels decreased, and the rates of spherical structure formation and organoid formation were significantly higher.However, ARRB1-/-mice failed to reverse the effect of 5-FU after ATPS treatment. Conclusion ATPS reverses 5-FU-induced intestinal mucositis through the protective effects of ARRB1 on intestinal barrier and organoid growth.