The development of nontoxic but effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that alpha-lipoic acid confers considerable radio-protective effect in mouse tissues when given prior to x-irradiation. In the present study, alpha-lipoic acid supplementation prior to x-irradiation with 4 and 6 Gy significantly inhibited the radiation-induced decline in total antioxidant capacity (TAC) of plasma. Radiation-induced decline in non-protein sulfhydryl content (NPSH) of different tissues, namely, brain, liver, spleen, kidney, and testis, was also ameliorated significantly at both 4 and 6 Gy doses. Maximal augmentation of radiation-induced protein carbonyl content was observed in spleen followed by brain, kidney, testis, and liver. Maximal protection in terms of carbonyl content was observed in spleen (116%) at 6 Gy dose, and minimal protection was found in liver (22.94%) at 4 Gy dose. Maximal increase in MDA (malondialdehyde) content was observed in brain, followed by testis, spleen, kidney, and liver. Protection by alpha-lipoic acid pretreatment in terms of MDA content was maximal in brain (51.67%) and minimal in spleen. The findings support the idea that alpha-lipoic acid is a free-radical scavenger and a potent antioxidant.