Objective:To investigate the effect of Tremella fuciformis polysaccharides(TFP)on oxidative damage induced by exhaustive exercise in mice and analyze its mechanism.Methods:L6 cells were treated with TFP for 48 hours,and the activity of L6 was detected by CCK-8 method.L6 cells were divided into three groups,including the control,H2O2,and H2O2+TFP groups,and incubated for 48 hours.LA levels were measured by a biochemical analyzer,and Nrf2,NQO1,and HO-1 protein levels were detected by Western blot assay.C57BL/6 mice were randomly divided into four groups(n=10 for each group),including model group and model+TFP group(50,100,200 mg/kg).The model+TFP groups were continuously gavaged with TFP,while the model group was gavaged with the same dose of distilled water once a day for two consecutive weeks.Exhaustive exercise was performed 30 minutes after the last administration,the duration of exhaustive swimming exercise was recorded,and enzyme-linked immunosorbent assay(ELISA)was used to detect liver glycogen(LG)and skeletal muscle glycogen(MG).ELISA was used to detect blood urea nitrogen(BUN),lactic acid(LA),ROS,malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),TNF-α,IL-6 and NF-κBp65 levels.Western blot assay was used to detect the levels of Nrf2,NQO1,and HO-1 proteins.Results:The LA levels of L6 cells in the H2O2 group were significantly(P<0.01)higher than those in the control group,while the protein levels of Nrf2,NQO1,and HO-1 were significantly(P<0.01)lower than those in the control group.TFP could significantly(P<0.01)reduce the LA levels in the culture medium and upregulate the expression of Nrf2,NQO1,HO-1 in L6 cells.TFP could significantly prolong exhaustive swimming time(P<0.01),reduce LA(P<0.01)and BUN(P<0.05,P<0.01)levels,increase liver and muscle glycogen levels(P<0.05,P<0.01),upregulate SOD(P<0.01)and GSH-Px(P<0.01),downregulate MDA(P<0.05,P<0.01)and ROS(P<0.01)levels,and reduce TNF-α(P<0.01),IL-6(P<0.01)and NF-κBp65(P<0.01).Compared with the model group,TFP could significantly increase Nrf2(P<0.05,P<0.01),HO-1(P<0.05,P<0.01)and NQO-1(P<0.05,P<0.01)protein expression levels.Conclusion:TFP improved oxidative damage caused by exhaustive swimming by inhibiting oxidative stress and inflammation,and its mechanism was related to regulating the Nrf2/HO-1 signaling pathway.