Abstract: AIM: To study the protective action of piperoethyl acetyl amine(PAA) against liver injury induced by acetaminophen in mice. METHODS: Mice were administered orally a dose or two doses of PAA and then given ip acetaminophen 110 mg.kg^-1. Serum transaminases(sALT, sAST), liver glutathione(GSH), liver microsomal cytochrome P-450 and blood acetaminophen concentration were determined. Damage of liver tissue was observed by light microscope. RESULTS: PAA markedly reduced the elevated sALT and sAST, and prevented the decrease of liver GSH in acetaminophen intoxicated mice. The damages of liver morphology such as inflammation and necrosis were also reduced. Blood acetaminophen concentration in mice treated with PAA 24 h before ip injection of acetaminophen was lower than that in control mice. In addition, 24 hours after administration of PAA remarkable increase of liver glutathione content was observed in mice. CONCLUSION: PAA is effective in protection against acetaminophen-induced liver damage through its effect on liver cytochrome P-450 and glutathione.