Abstract: Objective To explore the protective effect of crocin on myocardial ischemia reperfusion（MIR） rats through peroxisome proliferator-activated receptor γ（PPARγ）-cysteine containing aspartate specific protease-3（caspase-3）-polyadenylic acid diphosphate ribosyl polymerase（PARP） pathway. Methods Seventy-two rats were randomly divided into 6 groups: sham operation group, model group, low-, medium-and high-dose20, 40, 80 mg/（kg·d） crocin groups, crocin+PPARγ inhibitor T0070907 group crocin 80 mg/（kg·d）+T0070907 1.5 mg/（kg·d）. The MIR rat model was constructed by ligating the anterior descending coronary artery. After successful perfusion, the hemodynamic parameters of rats were determined, including left ventricular diastolic pressure（LVDP）, left ventricular end diastolic pressure（LVEDP）, maximum rate of increase/decrease of left ventricular pressure(dp/dt_max), the levels of serum and myocardial tissue lactate dehydrogenase（LDH）, creatine kinase isoenzyme（CK-MB）. Malondialdehyde（MDA） of rats were detected with kits. Pathological changes of rat myocardium were detected with hematoxylin-eosin（HE） staining method. Cardiomyocyte apoptosis of rats was detected with TdT-mediated dUTP nick and labeling（TUNEL） method. The expression of PPARγ-caspase-3-PARP pathway proteins in rat myocardial tissue was detected with Western blot. Results The myocardial fibers of rats in the sham operation group were arranged neatly, with no inflammatory cell infiltration in the interstitium, while the arrangement of myocardial fibers in the model group was disordered, with a large number of inflammatory cell infiltration in the interstitium. Compared with the model group, rats in the low-, medium-, and high-dose crocin groups had myocardial tissue pathology improvements, and the myocardial fibers in the middle-and high-dose crocin groups were arranged relatively neatly, with small amount of inflammatory cell infiltration. Rats in the crocin + T0070907 group had more severe damage of the myocardial tissues than those in the high-dose crocin group. Compared with the sham operation group, the hemodynamic parameters(LVDP, +dp/dt_max,-dp/dt_max), and the expression of PPARγ and B cell lymphoma 2（Bcl-2） in the model group were significantly reduced, while the LVEDP and the levels of serum and myocardial tissue LDH （2 762.74±317.69） vs（1 105.68±286.45） U/L, q=18.605, P＜0.001;myocardial tissue（4 852.34±244.82） vs（2 456.84±315.63） U/mg, q=29.820, P＜0.001, CK-MB and MDA, the cardiomyocyte apoptotic number, the expression of Bax, Cleaved caspase-3 and Cleaved PARP proteins were significantly increased（P＜0.05）. Compared with the model group, the LVDP, +dp/dt_max,-dp/dt_max, the expression of PPARγ and Bcl-2 proteins in the low-, medium-, and high-dose crocin groups were significantly increased, while the LVEDP, the levels of serum and myocardial tissue LDH, CK-MB and MDA, cardiomyocyte apoptotic number, and the expression of Bax, Cleaved caspase-3 and Cleaved PARP proteins were significantly decreased. Furthermore, with the increase of the dose of crocin, the changes appeared to be dose-dependent（P＜0.05）. T0070907 could reverse the protective effect of crocin on myocardial ischemia-reperfusion in rats. Conclusion Crocin may prevent myocardial injury in MIR rats by activating the PPARγ-caspase-3-PARP pathway.