Aim To investigate the effect of ranolazine postconditioning on myocardial apoptosis, the reperfusion injurysalvage kinase and the opening of MPTP in isolated rat hearts subjected to ischemia and reperfusion.Methods The langendorff mode was set up.Fifty-five SD rat hearts were randomly divided into 8 groups (n=7): ischema and reperfusion (I/R group),20 μmol·L~(-1) ranolazine postconditioning group(RPostC),ranolazine and the specific MPTP opener atractyloside group (RA), ranolazine and the specific ERK1/2 inhibitor PD98059 group (RP), ranolazine and the specific PI3K inhibitor PD98059 wortmannin group(RW), atractyloside group(A), PD98059 group (P) and wortmannin group (W). The isolated hearts were subjected to 30 minutes ischemia,10minutes drug postconditioning and 5 mitutes K-H buffer reperfusion.Myocardial apoptosis (TUNEL-positive cells), apoptotic index (AI), the opening of MPTP (spectrophotometry) and the The expression of p-AKT and p-ERK1/2 protein were measured at the end of reperfusion in each group.Results Compared with IR group, Myocardial AI and opening of MPTP were decreased in RPostC groups (P<0.05), the expression of p-AKT, p-ERK1/2 protein were increased in RPostC, RA, RP, and RW groups (P<0.05).There were no significant differences in other groups(P>0.05). Compared with RPostC group, Myocardial AI and opening of MPTP were increased in RA, RP, RW, A, P and W groups (P<0.05), and the expression of p-AKT、p-ERK1/2 protein were decreased in RP, RW, A, P and W groups (P<0.05). There were no significant differences of the expressions of p-AKT,p-ERK1/2 protein in RA groups (P>0.05). Compared with RA group, there were no significant differences in myocardial AI and opening of MPTP (P>0.05) and the expression of p-AKT and p-ERK1/2 protein were decreased in RP, RW, A, P and W groups (P<0.05).Conclusions Ranolazine postconditioning can attenuate myocardial apoptosis in isolated rat hearts subjected to ischemia and reperfusion via activation RISK pathway and inhibition of the opening of MPTP.