Abstract: In this study, the methanolic extract of Andrographis echioides (MEAE) was investigated for its hepatoprotective and antioxidant effects against acetaminophen induced hepatotoxicity in Wistar albino rats. The plant extract (200 and 400 mg kg-1, p.o./day for 10 days) showed a remarkable hepatoprotective and antioxidant activity. Hepatotoxicity was induced by acetaminophen at the dose of 750 mg kg-1 p.o. for 10 days. The serum marker enzymes such as aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphates (ALP), total bilirubin and liver gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) were significantly increased with a reduction of liver total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in acetaminophen induced rats. Treatment of rats with different doses of plant extract (200 and 400 mg kg-1, p.o.) significantly (p<0.001) altered serum marker enzymes and antioxidant levels to near normal against acetaminophen-treated rats. The activity of the extract at the different dose was comparable to the standard drug, silymarin (50 mg kg-1, p.o.). Extensive vascular degenerative changes and centrilobular necrosis in hepatocytes was produced by acetaminophen. Treatment with different doses of aerial parts of methanol extract of A. echioides produced only mild degenerative changes and absence of centrilobular necrosis, indicating its hepatoprotective efficiency. Results indicate that A. echioides possesses hepatoprotective and antioxidant effects against acetaminophen induced hepatotoxicity in rats. Thus, the study substantiates the hepatoprotective and antioxidant potential of methanol extract of A. echioides.