Myocardial ischemic reperfusion injury (MIRI) is a common complication of reperfusion therapy, such as early thrombolysis and coronary intervention after myocardial infarction, which seriously affects the prognosis of patients. Effectively reducing MIRI has always been an essential focus of medical workers. In addition to the analgesic effect, morphine can stimulate the heart and beyond the heart opioid receptors, especially the central nervous system, to trigger a myocardial protective effect. This review systematically summarizes the myocardial protective mechanisms involved in the central nervous system (lateral ventricle, intrathecal, and cephalic pulp extension ventrolateral areas) morphine preconditioning to regulate multiple mediators (adenosine, calcitonin gene‑related peptide, substance P, etc) for providing new ideas to the clinical use of morphine to improve myocardial ischemic reperfusion injury.