Introduction : Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) regioisomers, of which is determined by hemodynamic and pharmacological stimuli as well as by hypoxia. However, in addition to regulating vascular tone, EETs modulate several signaling cascades and affect cell proliferation, cell migration. In this process, EETs are implicated in the initiation of endothelial dysfunction of which the formation of reactive oxygen species is believed to play a critical role in inflammatory response. The epoxygenase CYP2C subfamily and CYP2J2 are expressed predominantly in the heart and coronary ateries, plays a role in the biosynthesis of EETs and postischemic functional recovery. Moreover, CYP2C8, CYP2C9 expression is upregulated by hypoxia and that the subsequent endothelial cell migration and tube formation. CYP inhibition abolished hypoxia-induced CYP 2J2 downregulation and upregulation of CYP 2C9, CYP4A and sEH. Moreover CYP inhibitor chloramphenicol induces the MMP-2, MMP-9 and VEGF. Endothelial cell migration and the degradation of extracellular matrix are essential steps in the angiogenic process. Meothods : Rat hearts were perfused in Langendorff mode with Krebs–Ringer buffer. Chloramphenicol(CAP, 300 關M) was added to the perfusion buffer 20 min before ischemia or upon reperfusion and no-flow ischemia was maintained for 30 min. CK release was determined by using the CK test kit. Rat heart microsomal protein was separated on 10% SDS-PAGE and transferred on PVDF membrane. Each protein blot were conjugated with corresponding antibody and detected by chemiluminescence detection kit. Results : CYP2C9, CYP4A, sEH, MMP-2 and MMP-9 expression were upregulated in Langendorff I/R rat heart model. Otherwise, CYP2J2 expression was reduced in this process. These CYP manifestations were reversed by CYP inhibitor CAP but not in the expression of MMP -2 and MMP-9, which was associated with the decrease of CK and infarct size. VEGF expression was increased after I/R injury, which was increased more by CYP inhibition. Conclusion : Cardioprotective effects of CYP inhibitor chloramphenicol were attributed to the downregulation of CYP2C9 and CYP4A and the upregulation of CYP2J2, and the availability of EETs. MMP-2 and MMP-9, which was leading to VEGF expression in I/R injury are not affected by CAP.These results indicate that CYP2J2 upregulation and EETs availability by CAP may play a role in angiogenesis in I/R injured rat heart.