Aim To explore whether paraoxon,an active component of organophosphate,can directly injure vascular endothelial cells in vitro and to explore the potential mechanisms. Method The thorac aortic rings of healthy sprague-dawley rats and cultured human umbilical vein endothelial cells(hUVEC) were exposed to medium contained different concentrations(36.3 nmol/L～36.3 μmol/L) of paraoxon and co-incubation different time.Both endothelial-dependent and non-dependent relaxation of aortic rings in rats and endothelial monolayer permeability in acetylcholine(Ach)-induced endothelium dependent relaxation(EDR) and increased hUVEC was assayed. Results Paraoxon concentration and time-dependently inhibited permeability of the endothelial monolayer in hUVEC.Paraoxon also simultaneously resulted in a reduction of both superoxide dismutase(SOD) activity and nitric oxide(NO) content and an increase of malondialdehyde(MDA) content in both aortic tissues and cultured cellular medium.But sodium nitroprusside-induced endothelium-independent relaxation of aortic rings were not affected by paraoxon.The injurious effects of paraoxon to EDR was partly lessened by added L-arginine,but not done by pretreatment of atropine. Conclusion Paraoxon could directly injure vascular endothelium cells and EDR.The mechanisms of endothelial dysfunction induced by paraoxon may relate to trigger oxidative stress and formation of lipid peroxidation by oxidation-stress,and the increase of endothelial cell monolayer permeability.