Objective:To explore the hepatoprotective and antioxidant effects of piperine against acetaminophen-induced hepatotoxicity in mice.Methods:In mice,hepatotoxicity was induced by a single dose of acetaminophen(900 mg/kg b.w.i.p.).Piperine(25 mg/kg b.w.i.p.) and standard drug silymarin(25 mg/kg b.w.i.p.) were given to mice,30 min after the single injection of acetaminophen.After 4 h,the mice were decapitated.Activities of liver marker enzymes [(aspartate transaminase(AST),alanine transaminase(ALT),and alkaline phosphatase(ALP)]and inflammatory mediator tumour necrosis factor-alpha(TNF-α) were estimated in serum,while lipid peroxidation and antioxidant status(superoxide dismutase,catalase,glutathione peroxidase, glutathione reductase,glutathione-s-transferase and glutathione) were determined in liver homogenate of control and experimental mice.Results:Acetaminophen induction(900 mg/kg b.w.i.p.) significantly increased the levels of liver marker enzymes,TNF-α,and lipid peroxidation,and caused the depletion of antioxidant status.Piperine and silymarin treatment to acetaminophen challenged mice resulted in decreased liver marker enzymes activity,TNF-αand lipid peroxidation levels with increase in antioxidant status.Conclusions:The results clearly demonstrate that piperine shows promising hepatoprotective effect as comparable to standard drug silymarin. Objective: To explore the hepatoprotective and antioxidant effects of piperine against acetaminophen-induced hepatotoxicity in mice. Methods: In mice, hepatotoxicity was induced by a single dose of acetaminophen (900 mg / kg bwip) .Piperine (25 mg / kg bwip) and standard drug silymarin (25 mg / kg bwip) were given to mice for 30 min after the single injection of acetaminophen. After 4 h, the mice were decapitated. Activities of liver marker enzymes [(aspartate transaminase (AST), alanine transaminase ), and alkaline phosphatase (ALP)] and inflammatory mediator tumor necrosis factor-alpha (TNF-α) were estimated in serum, while lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase and glutathione) were determined in liver homogenate of control and experimental mice. Results: Acetaminophen induction (900 mg / kg bwip) significantly increased the levels of liver marker enzymes, TNF-α, and lipid peroxidation, and ca used the depletion of antioxidant status. Piperine and silymarin treatment to acetaminophen challenged mice resulted in decreased liver marker enzyme activity, TNF-α and lipid peroxidation levels with increase in antioxidant status. Conclusions: The results clearly demonstrate that piperine shows promising hepatoprotective effect as comparable to standard drug silymarin.