Abstract: To explore the effect of quercetin on learning and memory in C57B /L mice fed high-fat diet and potential mechanism.45 female C57B /L mice were randomly divided into three groups: control group (normal diet) , high-fat diet group (about 20% fat) , quercetin group (high-fat diet supplemented with 0.01% quercetin) .Morris water maze experiment was conducted at the 26thweek.After that, mice were sacrificed.Then oxidative stress indexes in cortex and hippocampus were tested and the expression of NF-E2-related factor 2 (Nrf2) , Heme oxygenase-1 (HO-1) and Brain derived neurotrophic factor (BDNF) in hippocampus were evaluated by RT-PCR.Compared to the control group, there was a significant deficit in learning and memory in HFD group (p < 0.05) .The cortex and hippocampus of mice fed high-fat diet were exposed to significant oxidative damage (p < 0.05) .Furthermore, the expression of Nrf2, HO-1 and BDNF in hippocampus tissue decreased significantly (p < 0.05) in HFD group.After treated with quercetin, oxidative damage of cortex and hippocampus was alleviated.Additionally, the expression of Nrf2, HO-1 and BDNF were up-regulated and learning and memory was improved significantly (p < 0.05) .Quercetin could improve high-fat diet induced memory and learning impairment, which might be attributed to upregulate the expression of Nrf2, HO-1 and BDNF.