In the present study, we investigated the protective effect of the Lycii Fructus water extracts (LFE) against CCl4-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation, In addition, the pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE may be related to antioxidant effects and regulation of CYP2E1 gene expression.