The aim of our present study is to investigate the effect of Opuntia ficus indica f. inermis prickly pear juice (PPJ) against ethanol-induced liver injury in rats. Chronic ethanol administration (3 g/kg b.w.) during 90 days to Wistar rats, significantly (p < 0.01) increased the liver lipid and protein oxidation, reduced the glutathione content and the activities of liver antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and conversely elevated the liver injury biochemical markers like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase, cholesterol, triglycerides and caused a severe histopathologic injuries. Conversely pre-treatment of ethanol-fed rats with PPJ (20 and 40 ml/kg b.w., orally), interestingly reduced liver lipid and protein oxidation, histopathologic lesions and inhibited the alterations of antioxidant enzymes and the release of biochemical markers. The hepatoprotective effect of PPJ could be due to their capacity to end free radicals chain reactions or to enhance the endogenous antioxidants activities.