Background: Cytochrome P450 (CYP) enzymes are the third pathway of arachidonic acid metabolism and they play some roles in cardiovascular system. CYP2J2 is a CYP epoxygenase and produce epoxyeicosatrienoic acids(EET), which have vascular protective effects including vasodilation. CYP4A is a CYP hydroxylase, which produce hydroxyeicosatetraenoic acids(20-HETE), potent vasoconstrictors. We investigated the expression of CYP2J2 and CYP4A in type 2 diabetic rats. Method: Heart lysate and microsome of 24 week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and age-matched nondiabetic Long-Evans Tokushima Otsuka (LETO) rats as control were used. eNOS, CYP2J2 and CYP4A activities were measured by Western blot analysis and arachidonic acid metabolites by liquid chromatography. Result: eNOS, which reflects endothelial function was down-regulated in OLETF rats than control rats. eNOS activity of heart lysate of LETO rats was 100짹3% and 85짹6% in OLETF rats. CYP2J2 enzyme activity was underexpressed and CYP4A was overexpressed in OLETF rats compared with LETO rats in both heart lysate and microsomes(Figure). Conclusion: We found that diabetic rats have endothelial dysfunction and altered vascular homeostasis by measurement of CYP enzyme activities.