Aim:To examine whether isoliquiritigenin(ISL)can attenuate myocardial ischemia-reperfusion(MI/R)injury in rats by inducing metallothionein(MT)through acti-vation of janus kinase 2(JAK 2)/signal transducers and activators of transcription3(STAT 3)pathway.Methods:The experimental model of MI/R in rats was gener-ated by 30 min of ischemia and reperfusion for 2 h.The mRNA expression of MT,COX-2,and iNOS were measured by RT-PCR.The protein expressions of MT,JAK/STAT,extracellular signal-regulated kinase(ERK),and Akt were determinedby Western blotting in the absence or presence of a JAK kinase inhibitor,tyrphostinAG490(1.0 mg/kg,iv,1h before ischemia).Results:Pretreatment with ISL mark-edly decreased the severity of reperfusion-induced arrhythmias and myocardialinfarct size.In the ISL 20 mg/kg group,the activities of lactate dehydrogenase(LDH)and creatinine phosphokinase(CPK)were reduced by 38.4% and 51.3%when compared with the vehicle group.Increased JAK 2/STAT 3 phosphoryla-tion was accompanied by increased synthesis of MT but not of COX-2 or iNOS inISL-treated groups.AG490 can significantly weaken ISL-induced cardioprotectionand prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation.Conclusion:ISL protected MI/R injury through activation of JAK 2/STAT 3 sig-nal transduction pathway,which might be involved in mediating the upregulationof MT expression. Aim: To examine whether isoliquiritigenin (ISL) can attenuate myocardial ischemia-reperfusion (MI / R) injury in rats by inducing metallothionein (MT) through acti-vation of janus kinase 2 (JAK2) / signal transducers and activators of transcription3 3) pathway. Methods: The experimental model of MI / R in rats was gener- ated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX-2, and iNOS were measured by RT-PCR. Protein expressions of MT, JAK / STAT, extracellular signal-regulated kinase (ERK), and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 (1.0 mg / kg, : Pretreatment with ISL mark-edly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg / kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2 / STAT 3 phosphorylation was accomp anied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK2 / STAT3 phosphorylation.Conclusion: ISL protected MI / R injury through activation of JAK 2 / STAT 3 sig-nal transduction pathway, which might be involved in mediating the upregulation of MT expression.