Liver injury induced by viruses, toxic chemicals, certain drugs and environmental pollutants, has been on the increase for the past few decades and recognized as a toxicological problem. Nitrosamine compounds are known hepatic carcinogens. The present study was carried out to investigate the hepatoprotective effect of fish oil and virgin olive oil against diethylnitrosamine (DEN) intoxication in rats compared with drug (25mg/kg diet). Wister rats weighing 200 ± 5 g were induced hepatotoxicity by injection of DEN (via single intraperitoneally injection at 150 mg/kg/body weight). Rats were divided into 9 groups (n = 6) of non-hepatotoxicity, non-hepatotoxicity and treated, hepatotoxicity non-treated and hepatotoxicity treated with drug, fish oil, virgin olive oil. After 8 weeks the rats feeding with fish oil, virgin olive oil supplied to hepatotoxicity rats instead of diet significant improvement in lipid profile and liver function. However, a significantly increment in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSPx) and glutathione reduced (GSH) were observed in blood of hepatotoxicity rats treated with fish oil, virgin olive oil and mixtures. The treated groups showed a significant decrement in thiobarbituric acid reactive substances (MDA) in serum. Since the study of induction of the redox enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the fish oil and virgin olive oil. Treatment with fish oil and virgin olive oil reduces the histopathological liver abnormalities associated with hepatotoxicity. Moreover to the anti hepatotoxicity effect and possess antioxidant potential that may be used for therapeutic purposes suggested. The present study showed that fish oil, virgin olive oil were able to prevent or reduce the severity of diethylnitrosamine-induced liver injury.