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Objective:Paeoniflorin has antioxidative, antiinflammatory properties. In this study, weexamined its effectiveness against vascular oxidative stress, inflammation, andendothelial dysfunction in accelerated atherosclerosis.Methods:New Zealand white rabbits received an infusion of Paeoniflorin, after 6weeks high-cholesterol chow. Human umnilical vein endothelial cells (HCAECs)were incubated with Paeoniflorin before stimulation with oxLDL.Results:Paeoniflorin(2.5mg,5mg/kg) attenuated vascular oxidative stress significantlyand improved Endothelium-dependent relaxation(EDR).Paeoniflorin markedlyreduced vascular upregulation of ICAM-1 expression，plasma sP-selectin and ET-1concentrations；augmented vascular endothelial NO synthase activity, cyclic GMP(cGMP) content and plasma NO content (P<0.05 versus Control rabbits). In culturedendothelial cells, Paeoniflorin(5, 25, 50uM) increased eNOS phosphorylation atSer1177, leading to an increased production of nitric oxide. Furthermore, Paeoniflorinattenuated oxLDL induced generation of reactive oxygen species, caspase-3 activityand cellular apoptosis.Conclusion:Paeoniflorin protects against endothelial injury and enhances theendothelium-dependent vasodilatation, which is mediated in part through theactivation of eNOS, the inhibition of inflammation, the attenuation of oxidativestress and the decrease of endothelial cell apoptosis. Paeoniflorinor and its derivativesmay be useful for the treatment and/or prevention of atherosclerosis.