Background: Penthorum chinense Pursh (Penthoraceae, PCP), a well-known Miao ethnomedicine, has been tradition ally used to treat several liver-related diseases, such as jaundice and viral hepatitis. The alms of the present study were to evaluate the probable properties of the aqueous extract of PCP on carbon tetrachloride (CCl4-induced acute liver Injury In mice.& para;& para;Methods: C57BL/6 mice were orally administered an aqueous extract of PCP (5.15 and 10.3 g/kg BW) or silymarln (100 mg/kg) once dally for 1 week prior to CCl(4 )exposure. Silymarln serves as a positive drug to validate the effectlvenes of PCP.& para;& para;Results: A single dose of CCI4 exposure caused severe acute liver Injury In mice, as evidenced by the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alanine phosphatase (ALP), and the Increased TUNEL-positlve cells In liver, which were remarkably ameliorated by the pretreatment of PCP. PCP was also found to decrease the levels of malondlaldehyde (MDA), restore the glutathione (GSH) and enhance the activities of superoxide dismutase (SOD) and catalase (CAT) In the liver. In addition, the pretreatment of PCP Inhibited the degradation of hepatic cytochrome P450 2E1 (CYP2E1), up-regulated the expression of nuclear factor erythrold 2-related factor 2 (Nrf2) and Its target proteins In CCI4-treated mice.& para;& para;Conclusion: Results Indicated that the pretreatment of PCP (10.3 g/kg BW) effectively protected against CCI4-lnduced acute liver Injury, which was comparable to efficacy of silymarln (100 mg/kg). This hepatoprotective effects might be attributed to amelioration of CCI4-lnduced oxidative stress via activating Nrf2 signaling pathway.