We have recently showed that molecular hydrogen has great potential for selectively reducing cytotoxic reactive oxygen species, such as hydroxyl radicals, and that inhalation of hydrogen gas decreases cerebral infarction volume by reducing oxidative stress [I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K.-I. Katsura, Y. Katayama, S. Asoh, S. Ohta, Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nat. Med., 13 (2007) 688-694]. Here we show that the inhalation of hydrogen gas is applicable for hepatic injury caused by ischemia/reperfusion, using mice. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min, followed by reperfusion for 180 min. Inhalation of hydrogen gas (1-4%) during the last 190 min suppressed hepatic cell death, and reduced levels of serum alanine aminotransferase and hepatic malondialdehyde. In contrast, helium gas showed no protective effect, suggesting that the protective effect by hydrogen gas is specific. Thus, we propose that inhalation of hydrogen gas is a widely applicable method to reduce oxidative stress. (c) 2007 Elsevier Inc. All rights reserved.