Antiplatelet agents remain the cornerstone treatment in patients with ischemic heart diseases, as they decrease the mortality as well as the recurrence of cardiovascular complications. This study aimed to assess and compare the possible cardioprotective effect of cilostazol, clopidogrel and their combination in experimentally induced myocardial ischemia/reperfusion (MI/R) in rats.In this study ninety-six rats were divided into six equal groups (each of 16 rats): group 1, control normal received the vehicle; group 2, sham-operated and received the vehicle; group 3 (MI/R-treated) where myocardial infarction was induced by left coronary artery ligation (LCAL) for 30 min, followed by 2 h. reperfusion; group 4 received cilostazol (20 mg/kg, p.o.); group 5 received clopidogrel (30 mg/kg, p.o.); group 6 received combination of both drugs in the same doses. In all treated groups (groups 4, 5 & 6), drugs were administered for 3days, then they were exposed to MI/R. Results of the present study revealed that MI/R injury induced a significant decrease in mean arterial blood pressure (MABP), increase in heart rate (HR), elevation in T-wave voltage along with increased infarct size, plasma cardiac troponin I (cTnI) level and tumor necrosis factor alpha (TNF-α) and heart content ofmalondialdehyde (MDA), consequently with reduction in heart tissue glutathione peroxidase (GPx) activity. Cilostazol, clopidogrel or their coadministration exerted cardioprotective effect manifested by significant reductions in the T-wave voltage, infarct size and cTnI level via enhancement of antioxidant capacity and prevention of inflammatory and oxidative stress cascades. Additionally, cilostazol increased the HDL and decreased the LDL levels.  It could be concluded that cilostazol is an effective cardioprotective agentin treatment of myocardial infarction particularly when used as an adjuvant to clopidogrel.