Revascularization is currently the most effective method for the treatment of myocardial ischemia. However, in the process of treatment, reperfusion of ischemic area accelerates the apoptosis of damaged cardiomyocytes, aggravates myocardial ischemia and hypoxia, and leads to myocardial ischemia reperfusion injury (MIRI). NADPH oxidase-2 (Nox2) generates reactive oxygen species (ROS) to induce oxidative stress and cause myocardial oxidative damage. ATP-sensitive potassium channel (KATP) plays an important role in cardiac protection by regulating energy consumption during MIRI and reducing ROS production in myocardial cells after ischemia reperfusion. This article reviews the recent research progress of Nox2 and KATP mediated MIRI, and explores the regulatory role of KATP on Nox2 in ischemia reperfusion cardiomyocytes.