The results demonstrated that preconditioning with genistin remarkably improved the I/R-induced cardiac injury through inhibition inflammation and relieved the oxidative stress, whereas genistin affected the pathway of P2X7/NF-κB. Moreover, the treatment of genistin, which reduced the myocardial infarct size, may work as a cardioprotective agent. Here, P2RX7 is linked to myocardial infarction.