Reactive oxygen species (ROS) are involved in the pathophysiology of ischemia/reperfusion injury. To protect mouse hepatocytes from ischemia/reperfusion injury, we prepared two different sizes of citric acidprotected platinum nanoparticles (Pt-NPs), which exhibited ROS-scavenging activities and selective delivery to a specific type of liver cell. Small Pt-NPs (30 nm) reduced the superoxide anion, hydrogen peroxide, and hydroxyl radical levels in solution to a greater extent than did large Pt-NPs (106 nm). Large and small Pt-NPs predominantly accumulated in hepatic nonparenchymal cells after intravenous injection into mice. In a mouse model of ischemia/reperfusion injury, in which hepatic injury was induced by occluding the portal vein for 15 min followed by 6 h reperfusion, the increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities was inhibited by a bolus intravenous injection of either large or small Pt-NPs. However, small Pt-NPs inhibited the increase in these markers of hepatic injury to a greater extent than did large Pt-NPs. These results indicate that Pt-NPs can be used to prevent hepatic ischemia/ reperfusion injury. To our knowledge, this is the first report demonstrating the pharmacokinetics and efficacy of Pt-NPs to prevent hepatic ischemia/reperfusion injury.