Background: Diabetes mellitus is characterized by endothelial dysfunction and cardiovascular complications. Cytochrome P450 (CYP) 2J is the major epoxygenase expressed in cardiovascular system, which produces vasoprotective metabolites, EETs. PPAR-慣 is a key regulator of vascular biology, and is suggested to affect the metabolism of CYP. We examined the expression of CYP2J and PPAR-慣 in diabetic heart using OLETF rats. The response to fenofibrate, PPAR-慣 agonist, was also investigated. Methods: Twenty-eight diabetic OLETF and 28 non-diabetic age-matched LETO rats were randomly assigned into 4 groups, respectively. The activity of CYP2J3 and its major metabolite, 14,15-EET of rat heart at 36th week of age, and PPAR-慣 and CYP2J3 after administration of fenofibrate (150 mg/kg/day for 2 weeks) were measured using Western blot analysis and LC/MS. Results: Western blot analysis showed that the expression of CYP2J3 and PPAR-慣 was significantly down-regulated in OLETF group compared with LETO group (Figure, p<0.01). The level of 14,15-EET in OLETF rat heart was significantly lower than that of LETO on LC/MS (p<0.05). After administration of fenofibrate, the expression of both PPAR-慣 and CYP2J3 in OLETF rat heart was recovered to the similar level to those of control LETO group (Figure, p<0.01). Conclusion: Suppressed activity of PPAR-慣, CYP2J3, and EETs may contribute to cardiovascular complications in obese diabetic rats. We suggest that PPAR-慣 agonist, fenofibrate, restores the activity of CYP2J in diabetic rat heart.