Objective:To investigate and compare the hepatoprotective effects of crude ethanolic and aqueous extracts of Phyllanthus acidus (L.) Skeels (P. acidus) leaves on acetaminophen (APAP) and thioacetamide (TAA) induced liver toxicity in wistar rats. Silymarin was the reference hepatoprotective agent. Methods:In two different sets of experiments, the P. acidus extracts (200 and 400 mg/kg, body weight) and silymarin (100 mg/kg, body weight) were given orally for 7 days and a single dose of APAP (2 g/kg, per oral) or TAA (100 mg/kg, subcutaneous) were given to rats. The level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin and total protein were monitored to assess hepatotoxicity and hepatoprotection. Results:APAP or TAA administration caused severe hepatic damage in rats as evident from significant rise in serum AST, ALT, ALP, total bilirubin and concurrent depletion in total serum protein. The P. acidus extracts and silymarin prevented the toxic effects of APAP or TAA on the above serum parameters indicating the hepatoprotective action. The aqueous extract was found to be more potent than the corresponding ethanolic extract against both toxicants. The phenolic and flavonoid content (175.02±4.35 and 74.68±1.28, respectively) and 2,2-diphenyl-1-picrylhydrazil (DPPH) [IC50=(33.2±0.31)μg/mL] scavenging potential was found maximum with aqueous extract as compared to ethanolic extract. Conclusions:The results of present study suggests that the aqueous extract of P. acidus leaves has significant hepatoprotective activity on APAP and TAA induced hepatotoxicity, which might be associate with its high phenolic and flavonoid content and antioxidant properties.