The pathogenesis and progression of alcoholic liver disease (AID) are associated with free radical injury and oxidative stress, which could be partially attenuated by antioxidants and free radical scavengers. Quercetin, one of the most widely distributed flavonoids in plants, is a natural antioxidant. The hypothesis that quercetin could prevent the ethanol-induced oxidative damage in hepatocytes was investigated. The ethanol-intoxicated (100 mM for 8 h) rat primary hepatocytes were post-treated (2 h), simultaneously treated or pre-treated (2 h) with quercetin respectively, while the time-dependent (0.5-8 h) and dose-dependent (25-200 mu M) quercetin pre-treatment were used in the present study. The parameters of lactate dehydrogenase (LDH), aspartate transaminase (AST), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were determined to address the alterations of cell damage and antioxidant state after quercetin intervention. The toxic insult of ethanol to hepatocytes was challenged by quercetin and these parameters almost returned to the level of control group when hepatocytes were pre-treated with quercetin at the dose of 50 mu M for 2-4 h before ethanol exposure. In conclusion, quercetin pre-treatment provided protection against ethanol-induced oxidative stress in hepatocytes and may be used as a new natural drug for the prevention and/or treatment of ALD. (C) 2009 Elsevier Ltd. All rights reserved.