Hepatotoxicity by acetaminophen is the most frequent cause of acute liver failure in many countries. Prosopis farcta beans extract (PFE) has some antioxidant property and may alleviate hepatotoxicity. Therefore, the aim of this study was to evaluate effects of PFE against acetaminophen-induced hepatotoxicity.Thirty-six male Wistar albino rats weighing 220 ± 30 g were distributed into six groups. Two groups were pretreated with PFE (50 and 75 mg/kg) for 7 days before administration of acetaminophen (600 mg/kg). Two were given acetaminophen or PFE (50 and 75 mg/kg) alone, and the control received normal saline. One day after acetaminophen, administration blood samples were collected by cardiac puncture to determine liver function enzymes markers; aspartate aminotransferase and alanine aminotransferase (AST and ALT), cholesterol, triglyceride (TG), high, low, and very low density lipoproteins (LDL and VLDL).In acetaminophen-treated rat plasma AST (314 ± 18.54 vs. 126.37 ± 4.13), ALT (304 ± 49.24 vs. 187.33 ± 3.71), cholesterol, TG, LDL, and VLDL were increased by 149, 160, 37, 92, 60, and 94%, respectively. PFE at both doses significantly (P < 0.05) attenuated the above biochemical indices to near normal.Prosopis farcta beans extract (50 and 75 mg/kg) exhibited hepatoprotective activity against APAP.