Introduction: Acetaminophen, one of the most commonly used analgesic and antipyretic drugs, is characterized by its hepatotoxic effects after prolonged administration, due to the excessive formation of intermediate N-acetyl-p-benzoquinone imine, a product of phase I metabolism. Because of their chemical composition and antioxidant activity, Morus nigra L. leaves display therapeutic activity. Objectives: Evaluate the hepatoprotective effect of Morus nigra L. hydroalcoholic extract on acetaminophen-induced liver damage in rats. Methods: Twenty rats (Rattus norvergicus albinus) were distributed into four groups: control, acetaminophen (250 mg/kg) as hepatotoxicity control group, acetaminophen + silymarin (100 mg/kg) and acetaminophen + Morus nigra L. (250 mg/kg). Liver function enzymes ALT and AST were measured on days 1, 6, 12 and 21. Additionally, a histopathological study was conducted of liver sections. Results: Acetaminophen raised ALT and AST levels, which remained high after administration of distilled water as placebo until day 21. Silymarin and Morus nigra L. leaf extract lowered ALT and AST levels to values similar to the control (baseline). Conclusions: Results show that administration of Morus nigra L. improves the hepatic lesion caused by acetaminophen with an effect significantly similar to that of silymarin.