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Ischemia/reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. The effect of longan flower ethyl acetate extract (LFEE) on hepatic I/R injury in rats was examined. Aspartate aminotransferase, alanine aminotransferase, hepatic thiobarbituric acid reactive substances (TBARS), interleukin-1β, interleukin-6, interleukin-10, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 activities were significantly increased after I/R injury, but decreased in the groups with LFEE treatment. Significant decrease in hepatic glutathione levels after I/R injury was observed upon LFEE treatment. NADPH:quinone oxidoreductase 1 activity was significantly increased after I/R injury, and it was further increased in the groups with LFEE treatment. Histological results indicated that LFEE was effective in improving liver tissue morphology during I/R injury. Therefore, LFEE might offer a novel intervention for patients suffering from I/R of the liver especially in the process of hepatotomy and liver transplantation.