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Background: Genistein is a soya isoflavone, which is found naturally in legumes, such as soybeans and chickpeas. Radiation–induced free radicals in turn impair the antioxidative defense mechanism, leading to an increased membrane lipid peroxidation that results in damage of the membrane bound enzyme and may lead to damage or death of cell. Hence, the lipid peroxidation is a good biomarker of damage occurs due to radiation and the inhibition of lipid peroxidation is suggestive of radioprotective action. Glutathione has been shown to protect cells against oxidative stress by reacting with peroxides and hydroperoxides and determines the inherent radiosensitivity of cells. Materials and Methods: For experimentation, healthy Swiss Albino male mice of 6 -8 weeks old were selected from inbred colony. Genistein was dissolved in dimethyl sulfoxide and then prepared different concentration solutions so that the volume administered intraperitoneally was 0.5 ml. Lipid peroxidation was estimated by the method of Ohkawa and GSH was estimated by the method of Moron. Results: The intraperitoneal administration of optimum dose (200 mg/kg body weight) of Genistein before 24 hrs and 15 minutes of irradiation (8 Gy at a dose rate of 1.02 Gy/min) reverted the increase in lipid peroxidation (by 18.01% ± 3.05) and decrease of Glutathione (by 62.05% ± 21.58) caused by irradiation in liver of Swiss albino mice. Statistically analyzed survival data produced a dose reduction factor (DRF) = 1.24. Conclusion: The results indicate that Genistein against radiation effect may pave way to the formulation of medicine in radiotherapy for normal tissue and possible against radiomimetic drug induced toxicity. Iran. J. Radiat. Res., 2009 7 (4): 187-199