Background: Based on the effect of substance possessing antioxidant effect previously reported, it was hypothesized that lycopene extracted from tomato (Tomato pomace), a substance possessing antioxidant activity, might be able to protect against oxidative stress induced by either carbon tetrachloride or gamma radiation. Materials and Methods: A total of 72 experimental male albino rats were randomly divided into equal six groups of twelve rats each. Group 1: served as the control group. Group 2: rats were administrated with (5 gm) tomato extract/kg body weight by gastric lavage tube for 15 days. Group 3: rats were exposed to single dose (10 Gy) whole body gamma irradiation. Group 4: rats were administered with CCl4 only in groundnut oil (1:1) at a dose of 3 ml/kg body weight by single intraperitoneal administration. Group 5: rats were treated with lycopene extract for 15 days before exposure to single dose (10 Gy) whole body gamma irradiation. Group 6: rats were treated with lycopene extract for 15 days before administered with CCl4 for 15 days. Results: showed highly significant increase in activities of alanine transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) in serum, 24 hours after CCl4 administration or radiation exposure. Highly significant decrease in activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) content in the brain tissues. Meanwhile, highly significant increase in MDA content in the brain tissues. Supplementation with lycopene before CCl4 intraperitoneal administration or radiation exposure, exerted marked amelioration of CCl4 and ionized radiation induced disturbances in all the investigated parameters. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after lycopene administration. Therefore, lycopene could have a beneficial role in modulating oxidative stress by improving the natural antioxidant mechanism. Conclusion: Administration of lycopene by using suitable stomach tube pre-CCl4 intraperitoneal administration or gamma irradiated has significantly ameliorated the disturbances induced in all the investigated parameters.