Myocardial ischemia-reperfusion (I/R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Myocardial ischemic postconditioning (PostC) is a strong endogenous cardioprotective phenomenon, which targets the increased tolerance of the myocardium against I/R. It has been reported that protective effects of PostC decrease/disappear with age and chronic heart disease. Similarly low serum melatonin levels have been reported in the same risk groups. Irisin is a thermogenic protein and it is thought to play regulatory role in energy metabolism in the pathogenesis of myocardial infarction. The aim of this study was to investigate the effects of PostC and physiological and pharmacological concentrations of melatonin on I/R induced change of irisin using an in vivo model of myocardial I/R injury. Rats were pinealectomized (Px) or sham-operated (non-Px) (control) 2 months before the I/R studies. In order to produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Melatonin was administrated by intraperitoneal injection last 10 days (10 mg/kg). PostC was induced by 3 cycles of R/I (10 s each) after the ischemia. Irisin level was detected by qRT-PCR. The levels of the irisin increased with I/R (20%) and Px (92%), decreased with PostC and melatonin both Px and non-Px groups. Additionally, it decreased with applications of melatonin and PostC together in Px group. These results suggest that irisin level may increase with Px and cardiac I/R injury and decrease with melatonin and PostC. Irisin may play an important role in cardioprotection of ischemic PostC and physiological and pharmacological concentration of melatonin. This study is supported by TUBITAK (115S323)