AimTo investigate whether C-reactive protein (CRP) accelerated the onset of endothelial progenitor cell (EPC) senescence and whether fenofibrate can antagonize the effects of CRP.Furthermore, this study aims to explore the possible mechanisms responsible for CRP on EPCs.MethodsEPCs were incubated with different concentration of CRP（1 mg/L, 2.5 mg/L, 5 mg/L）and 10 μmol/L fenofibrate.After exvivo cultured for 7 days, EPCs became senescent as determined by acidic β-galactosidase staining.To get further insights into the underlying mechanisms of these effects induced by CRP and fenofibrate, we measured human telomerase reverse transcriptase (hTERT) mRNA expression and determined the endothelial nitric oxide synthase (eNOS) by using western blotting.Results(1) CRP dose-dependently accelerated the onset of EPCs senescence in culture.Moreover, fenofibrate can inhibit CRP-induc se- expression.However, fenofibrate can up-regulate the expresse of hTERT mRNA in EPCs and up-regulate the expression of eNOS protein in EPCs.Conclusions(1)CRP accelerated the onset of EPCs senescence, leading to cellular dysfunction.The effect of CRP might be dependent on telomerase inactivation, and eNOS also appeared to play a major role.(2)Fenofibrate prevents effect against CRP-induced EPCs senescence.