Objective To investitate the efficacy of cannabinoid-2 receptor (CB2R) activation in preventing liver ischemia-reperfusion (I/R) injury in mice.Methods Forty-eight male C57BL/6J mice,weighing 20-30 g,were divided into 4 groups (n =12 each):sham operation group (group S),group I/R,CB2R agonist JWH133 group (group J),and CB2R agonist JWH133 + CB2R antagonist SR144528 group (group JS).Liver I/ R was produced by blocking the hepatic artery and portal vein for 30 min followed by 45 min of reperfusion in anesthetized mice.At 60 min before ischemia,JWH133 20 mg/kg was injected intraperitoneally in group J,and JWH133 20 mg/kg and SR144528 30 mg/kg were injected intraperitoneally in group JS.The liver was removed at 45 min of reperfusion for determination of tumor necrosis factor-α (TNF-α),macrophage inflammatory protein-1α (MIP-1α) and MIP-2 contents (using ELISA),and expression of TNF-α,MIP-1α,MIP-2 and intercellular adhesion molecule-1 (ICAM-1) mRNA (by RT-PCR) in the liver tissues and for microscopic examination of the pathological changes.Results Compared with group S,the contents of TNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in J and JS groups.Compared with group I/R,the contents of TNF-α,MIP-1α and MIP-2 were significantly decreased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was down-regulated in J group,and no significant change was found in the parameters mentioned above in JS group.Compared with group J,the contents ofTNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in JS group.The pathological changes of liver tissues were significantly attenuated in group J as compared with I/R and JS groups.Conclusion CB2R activation is effective in preventing liver I/R injury in mice and the mechanism is related to inhibitioni of inflammatory responses in liver tissues.