Objective To investigate the effect of SIRT1 on Nrf2/HO-1 signaling pathway and the protective effect of resveratrol (RSV) in myocardial ischemia/reperfusion injury (MI/RI). Methods Sixty healthy male SD rats were randomly divided into 4 groups(n=l 5)：sham operation(groupS),group I/R,resveratrol preconditioning(group R),resveratrol preconditioning+ex527(group RE).R group and RE group were intraperitoneally injected with RSV 15 mg/Kg 1day/day for 7 days before the establishment of model,S group and I/R group were intraperitoneally injected with normal volume of saline；RE group was injected with SIRT1 inhibitor ex527 1μg/kg at 15 minutes before ischemia.Myocardial I/R was produced by occlusion of left coronary anterior descending artery for 30 min followed by 120 min reperfusion..Monitors continuously monitored and recorded the basis of heart rate (HR)，mean arterial pressure(MAP) and rate—pressure product(RPP) before ischemia(T1)120 min after reperfusion(T2).Blood samples were maken for detecting the concentration of LDH and CK-MB by ELISA at the end of reperfusion.The rats were then killed in each group,and the heart was removed for measurement of myocardial infarct size by using TTC staining.The heart was removed for measuring content of MDA and activity of SOD.The expression of myocardial SIRT1，Nrf2，HO-1 mRNA and protein were measured（by PCR and Western blot analysis). Results Compared with the basic (T1) of HR,MAP,and RPP before ischemia in each group(group I/R，group R，group RE)，after the reperfusion(T2)：HR，MAP and RPP reduced(P<0．05)；Compared with the group I/R ，after the reperfusion(T2)，HR，MAP and RPP in group RE increased(P<0．05)；Compared with group S，the levels of LDH，CK-MB in serum and the infarct size were significantly increased，the content of MDA was increased and the activity of SOD was decreased，the expression of SIRT1，Nrf2，HO-1 mRNA and protein were also significantly increased in group I/R，group R，group RE(P<0．05)．Compared with group I/R ,the levels of LDH，CK-MB in serum and the infarct size were significantly decreased,the content of MDA was decreased and activity of SOD was increased,and the expression of SIRT1,Nrf2,HO-1 mRNA and protein were also significantly increase in group R(P<0.05)．There was no significant difference in the above changes between group I/R and RE （P>0．05)．Compared with group R，the levels of LDH，CK-MB in serum and the infarct size were significantly increased,the content of MDA was increased and activity of SOD was decreased,the expression of SIRT1Nrf2,HO-1 mRNA and protein were also significantly decreased in group RE(P<0.05). Conclusions SIRT1 activates the Nrf2/HO-1signaling pathway which is involved in RSV attenuates MI/RI and reduces oxidative stress.