Abstract: Aflatoxin B₁(AFB₁),one of toxic metabolites produced by Aspergillus flavus and Aspergillus parasiticus,is the most toxic mycotoxin widely present in corn,peanut and other agricultural products. QUE is a flavonoid compound that has physiological effects such as anti-oxidation. This study was to investigate the protective effects of quercetin on rat hepatocytes induced by AFB₁ and its mechanism. CCK-8 results showed that the half maximal inhibitory concentration(IC₅₀)of AFB₁ against normal rat liver cells(BRL cells)was 23 μmol/L,while QUE treatment at a concentration less than 15 μmol/L did not produce significant damages to the cells. When the cells were pretreated with QUE for 24 h,followed by AFB₁ treatment for another 24 h,the cell proliferative ability and levels of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione s-transferase(GST)were measured. The results showed that QUE enhanced intracellular SOD and GST enzyme activity,improve the cell's own antioxidant activity,and reduce the oxidative damage of MDA and ROS induced by AFB₁,thereby keeping cell viability. Furthermore,AFB₁ treatment significantly increased the expression of the pro-apoptotic gene Bax(p<0.05),but dramatically(p<0.05)decreased the expression of AKT,Nrf2 and HO-1.On the contrary,QUE pretreatment significantly(p<0.05)increased the expression of AKT,Nrf2,HO-1 and Bcl-2,demonstrating the protective effect of QUE against the AFB₁-induced cytotoxicity. Therefore,to a certain extent,quercetin has some protective effect on the toxic injury of AFB₁-induced in rat hepatocytes.