Background:Although statin therapy suppresses cardiovascular events based on arteriosclerosis, residual risks including hypertriglycemia still remain. Recently, a specific peroxisome proliferator-activated receptor-? modulator (SPPARM?), pemafibrate (K-877), was developed, and presented beneficial effect on lipid control. However, effect of K-877 on vascular function remains unknown. Here, we examined the effects of K-877 on vascular inflammation and endothelial dysfunction in diabetic mice.Methods:Diabetes was induced to seven-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). K-877 (0.3 mg/kg/day) was administered orally to diabetic mice fed a normal chow for 3 weeks. The non-treated mice received vehicle. Endothelium-dependent or endothelium-independent vascular response was analyzed by acetylcholine or sodium nitroprusside, respectively, using aortic rings obtained from our mice. Human umbilical vein endothelial cells (HUVEC) were used for in vitro experiments.Results:K-877 administration did not affect body weight and cholesterol levels, however it significantly reduced triglyceride level (P<0.05) in diabetic mice. Endothelium-dependent vascular response was impaired by the induction of diabetes, however, it was significantly ameliorated by K-877 (P<0.05) compared with vehicle in diabetic mice. Endothelium-independent vascular response did not differ among our animals. In in vitro experiments, 0.1 ?M K-877 reduced the expression of ICAM-1 (P<0.05) and e-selectin (P<0.05) in TNF-? stimulated HUVEC.Conclusion:K-877 attenuated vascular dysfunction and inflammatory activation of endothelial cells. These results suggested that K-877 may attenuate diabetes-induced endothelial dysfunction, leading to the prevention of cardiovascular complications in patients with diabetes mellitus.