Aim It was presumed that Chronic orally organophosphorus insecticide may consume PON1 and result in development of atherosclerosis.The aim of the present study was to explore whether chronic orally organophosphorus insecticide trichlorfon has a similar or aggravating atherogenic effect of hyperlipidic diet and analyze the possible mechanisms.Methods 32 healthy male New Zealand rabbits were divided randomly into 4 groups with 8 rabbits in each group.They were fed a standard normal chow,normal chow plus trichlorfon 18 mg/(kg·d),the hyperlipidic(50 g/d)chow which containing 1% cholesterol and 7.5% yolk powder and 8% lard and trichlorfon plus hyperlipidic chow respectively.After 70 days,rabbites were sacrificed,the function,parameters of both biochemistry and pathohistology in isolated vesseles and blood were analyzed.Results The treatment of trichlorfon and hyperlipidic diet resulted in a significant inhibition of the ACh-induced endothelium-dependent relaxation response,but did not in sodium nitroprusside induced endothelium-independent relaxation in isolated aortic rings from rabbits,a significant decrease of activity of both paraoxonase and superoxide dismutase and a significant increase of concentration of malondialdehyde in sera.An activity of cholinesterase was markedly decreased in the alone trichlorfon treated group,but was significantly increased in hyperlipidic diet group.Hyperlipidic diet resulted in pathologic changes of atherosclerosis examined by light microscopy including that the vascular intima become more rough and thicker than normal,a lot of lipid foam cells migrated to regions under intima interval and smooth muscle cells were arranged in more disorder than normal group,trichlorfon alone did not,but aggravated significantly those changes induced by hyperlipidic diet.Conclusion A long time orally trichlorfon could result in injuries of vascular endothelial function and accelerate atherogenic effects of hyperlipidic diet.The mechanism may be related to the decrease of PON1 activity in sera and oxidative stress reaction induced by trichlorfon.