To explore the effect of Fomes officinalis Ames polysaccharides (FOPS) on anti-oxidative stress,and study its mechanism from the Nrf2/ARE signaling pathway.Seventy two eligible male SD rats were weighed and divided into sham control group,AD model group,donepezil hydrochloride group (0.5 mg/kg),FOPS high,medium and low dose groups (100,50,25 mg/kg),with 12 rats in each group.The AD rat model was established by injecting (5 μL/side) Aβ_1-42 in the hippocampal CA1 area of both sides of the rat.After 30 days of treatment,The learning and memory ability was tested by Morris water maze.RT-qPCR and Western blotting were used to detect the structural proteins Keap1,Nrf2 and the downstream antioxidant protein HO-1,NQO1 mRNA and protein content in the cerebral cortex and hippocampus of each group.It was found that,After intervention 30 days，compared with blank group,The learning and memory ability of rats in AD model group decreased significantly (P<0.01),The mRNA content and protein expression of Nrf2,NQO1,HO-1 in hippocampus and cerebral cortex of rats decreased significantly (P<0.01),while Keap1 mRNA content and protein expression increased significantly (P<0.01).Compared with the AD model group,the learning and memory abilities of rats in the donepezil hydrochloride and high,medium-dose groups of FOPS were significantly increased (P<0.01).The mRNA content and protein expression of Nrf2,NQO1,HO-1 in the hippocampus and cerebral cortex of rats was significantly increased (P<0.05,P<0.01),Keap1 mRNA content and protein expression were significantly reduced (P<0.05,P<0.01).In conclusion FOPS promoting the nuclear translocation of Nrf2 by regulating the expression of Keap1,inducing the expression of NQO1 and HO-1,and play a role in improving the bodys antioxidant damage,thereby improving the learning and memory ability of AD rats.