RATIONALE: Previous studies indicate that molecular hydrogen (H2) is an efficient antioxidant gas that reaches rapidly across cell membranes and selectively reduces the hydroxyl radical (.OH), the most cytotoxic reactive oxygen species (ROS), and suppresses oxidative stress-induced injury in several organs. Since oxidative injury, especially hydroxyl radical, is implicated in radiation-induced tissue damage to the lung, we studied the effect of H2 as pulmonary radio-protectors in mice. METHODS AND MATERIALS: C57/bl6 female mice received 18Gy single-dose irradiation to the thorax. One cohort also was received the H2 treatment, as being inhaled of 4% H2 gas during irradiation period and drunk H2 containing water (0.8mM H2) after irradiation period. Subgroups were evaluated at variable time-points (1,3,7 days and 3 month post irradiation) for acute and late radiation lung damage. RESULTS: Within 7 days post-irradiation as acute lung damage phase, control irradiated mice had marked accumulated positive cells in bronchial epithelial cells for 8-OH-dG, ssDNA and TUNEL staining as markers for oxidative stress and apoptosis, less seen in irradiated, H2-treated mice. Consistent with these results, reduced malondialdehyde (MDA) levels and reduced expression level of nitrotyrosin, Bax and TGF-beta1 were also seen in lung tissue from irradiated mice with H2 treatment within 7 days post-irradiation, when compared with those of control irradiated mice without H2 treatment by western blotting and MDA assay. At three month post-irradiation, control irradiated mice had lung fibrotic findings as late lung damage, less seen in irradiated mice with H2-treatment by analysis as Ashcroft Score histologically. CONCLUSION: Our results indicate that H2 treatment can reduce oxidative stress in radiation-induced tissue damage to the lung and could be useful therapy for protection in radiation lung injury, owing to its selective reaction with cytotoxic ROS without known toxic side effects.