AIM: Hepatic ischemia/reperfusion injury may cause acute inflammatory, significant organ damage or dysfunction, and remains an important problem for liver transplantation.Our previous in vivo and in vitro studies demonstrated that Yisheng injection (YS), a traditional Chinese medicine, had protective effect on ischemia/reperfusion injury. In this study, we examined whether YS had protective effect for hepatic ischemia/reperfusion injury and explored its protective mechanism.METHODS: Hepatic warm ischemia/reperfusion was induced in mice. YS at different doses (5, 10, 20 mg/kg)was injected intraperitoneally 24 h and 1 h before ischemia and a third dose was injected intravenously just before reperfusion. The hepatocellular injury, oxidative stress,neutrophil recruitment, proinflammatory mediators and adhesion molecules associated with hepatic ischemia/reperfusion injury were assayed by enzyme-linked immunosorbent assay (ELISA), immunohistochemical assay and reverse transcription polymerase chain reaction (RT-PCR).RESULTS: Undergoing 90 min of ischemia and 6 h of reperfusion caused dramatical injuries in mouse livers.Administration of YS at doses of 5, 10 and 20 mg/kg effectively reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), from 3 670±463 U/L, 2 362±323 U/L and 12 752±1 455 U/L in I/R group to 1 172±257 U/L,845±193 U/L and 2 866±427 U/L in YS (20 mg/kg) treated group, respectively (P＜0.01). The liver myeloperoxidase (MPO) and malondialdehyde (MDA) contents were decreased from 1.1±0.2 (U/mg protein) and 9.1±0.7 (nmol/mg protein) in I/R group to 0.4±0.1 (U/mg protein) and 5.5±0.9 (nmol/mg protein) in YS (20 mg/kg) treated group, respectively (P＜0.01). Moreover, the serum levels of tumor necrosis factor-alpha (TNF-α) were reduced from 55±9.9 (pg/mL) in I/R group to 16±4.2 (pg/mL) (P＜0.01).Furthermore, the over-expressions of TNF-α and intercellular adhesion molecule-1 (ICAM-1) were suppressed by YS treatment in a dose-dependent manner.CONCLUSION: YS attenuates hepatic warm ischemia/reperfusion injury by reducing oxidative stress and suppressing the over-expression of proinflammatory mediators and adhesion molecules.