The impact of sex hormones on different mechanisms involved incalcium loading during myocardial ischemia reperfusion injury wasstudied through investigating the effect of L-type calcium channelblocking, sarcoplasmic reticulum calcium ATPase pump inhibition andNa+ / H+ exchange inhibition mechanisms. 120 adult albino rats wereused in this study. 60 rats were females (50%) and 60 rats were males(50%); the animals were classified into 12 study groups each of themconsisted of 10 rats. Rat hearts were isolated, perfused with Krebs-Heneseleit buffer solution and subjected to ischemia reperfusion.Gonadectomy of male rats improves myocardial function & decreasedmyocardial cell damage, apoptosis, and calcium overload after ischemiareperfusion injury. Also Supraphysiological testosterone administrationto male gonadectomized rats resulted in a significantly higher functionalrecovery of the myocardium & a significantly lower apoptotic,myocardial injury parameters and cytosolic calcium levels after ischemiareperfusion injury. Gonadectomy of female rats caused deterioration inthe left ventricular functional parameters associated with increasedmyocardial cell injury, apoptotic parameters and cytosolic calcium levels.Estrogen substitution in female gonadectomized rats significantlyimproved the left ventricular functional parameters which was associatedwith less myocardial damage, less apoptosis and decreased cytosoliccalcium levels. Moreover, female hearts can tolerate ischemia reperfusioninjury more than male hearts.