Objective:To study the protective effects of exo-polysaccharide of Rhodotorula mucilaginosa on drug-induced liver injury in mice and analyze its potential molecular mechanism, so as to provide scientific basis for the application of exo-polysaccharide of Rhodotorula mucilaginosa in functional food and drugs.Methods:Based on the antioxidant activity of polysaccharides, the effects of exo-polysaccharide component RmEPS-11 from Rhodotorula mucilaginosa on liver toxicity induced by INH and RIF in mice were evaluated.Results:Compared with the mice treated with INH and RIF, the levels of ALT and AST in serum and the content of MDA in liver were significantly decreased, while the activity of SOD and the content of GSH in liver were significantly restored. In addition, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly improved. The mechanism study showed that the protective effect was mainly due to the regulation of CYP2E1 mRNA expression level, resulting in the reduction of harmful free radicals and ROS formation, accompanied by the significant induction of antioxidant capacity.Conclusion:The polysaccharide RmEPS-11 extracted from R. mucilaginosa CM-1 can protect mice from acute liver injury induced by INH and RIF.