Herbs are known to play a vital role in the management of various liver diseases. Garlic oil (GO) contains numerous organosulfur compounds with potential hepatoprotective effects. The present work was planned to evaluate the possible preventive role of GO on biochemical and histopathological alterations induced by combined administration of ethanol (EOH) and carbon tetrachloride (CCl4) in rat liver. Two dose levels of GO (5 or 10 mg/kg/day) were administered orally to rats for 7 consecutive days with EOH + CCl4-induced liver damage. Activity of GO against liver damage was compared with that of silymarin (25 mg/kg/day, p.o. for 7 consecutive days). Biochemical parameters including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (γ–GT), alkaline phophatase (ALP) and bilirubin were estimated to assess the liver function. In addition, the level of total proteins, triglycerides, total cholesterol, glutathione (GSH), and thiobarbituric acid reactive substances (TBARS), in liver tissues were estimated. Liver damage was evidenced by an increase in the activity/level of AST, ALT, γ-GT, ALP and bilirubin in sera of rats after the combined administration of EOH and CCl4 compared to normal animals. Pretreatment of rats with GO reduced the EOH + CCl4-induced elevated levels of the above indices. Similarly, GO significantly prevented the decline in total proteins and the increase in triglycerides and total cholesterol resulted after EOH + CCl4 administration in rat liver homogenates. In addition, GO pretreatment restored liver GSH levels decreased due to EOH + CCl4 administration. The elevation in liver TBARS level due to EOH + CCl4 administration was also prevented by pretreatment with both low and high doses of GO. Histopathological examination indicated that GO exhibited an obvious preventive effect against the centrilobular necrosis and nodule formation induced by EOH + CCl4 administration. In conclusion, GO exerts hepatoprotective actions against EOH + CCl4-induced toxicity in rats.