Introduction : Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid (AA) to epoxyeicosatrienoic acid (EET) regioisomers, of which is determined by hemodynamic and pharmacological stimuli as well as by hypoxia. During myocardial ischemia / reperfusion (I/R) injury, AA metabolism is increased and EETs may have a cardioprotective effect, however, few data have been exactly shown for changes of various CYP isoforms in this process. Therefore, we examine the effects of CYP inhibitor sulfaphenazol on the expression of CYP2C9, CYP4A and CYP2J2 in I/R injured SD rat heart. Meothods : Rat hearts were perfused in Langendorff mode with Krebs–Ringer buffer. Sulfaphenazole (300 關M) was added to the perfusion buffer 20 min before ischemia or upon reperfusion. No-flow ischemia was maintained for 30 min, and reperfusion was accomplished by restoring flow for 15 min for CK release determination by using the CK test kit, and infarct size determination by triphenyl tetrazolium chloride stainindihydroethidium staining after 60 min. Results : I/R injury upregulate the CYP monoxygenase CYP2C9 , CYP4A and sEH expression leading to increase of CK release and infarct size and downregulate CYP2J2 expression in a Langendorff isolated perfused rat heart model. CYP inhibitor sulfaphenazol administration at reperfusion in Langendorff I/R reverse the expression of CYP2C9, CYP4A, sEH and CYP2J2. Moreover CK release (I/R injury 1.84 짹 0.22 VS, I/R + SPZ 1.05 짹 0.26, U/15 min, p < 0.01) and infarct size (I/R injury 43.70 짹 6.210 : I/R + SPZ 18.42 짹 5.42, p < 0.01) was reduced by sulfaphenazol. Conclusion : These alteration of CYP monoxygenase after myocardial ischemia was reversed by CYP inhibitor sulfaphenazol and CK release and infarct size were also reduced. These data indicate CYP inhibitor sulfaphenazol have a critical role in cardioprotective effect in myocardial I/R injury by regulating CYPs expression.