Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.