Abstract： Objective To investigate the mechanism of endothelial cell damage under insulin resistance state induced by high fat-feeding by observations of the effects of antioxidant N-acetylcysteine(NAC) on the blood glucose,lipids,the histological parameters of aorta,and the expression of intercellular adhesion molecules-1(ICAM-1),monocyte chemoattractant protein-1(MCP-1) and NF-κB/IκBα in aortic intima.Methods Forty-five Wistar male rats aged 5 to 6 weeks were randomly divided into 3 groups:control,high fat-feeding(HF) and HF plus NAC treatment(HF+NAC).Blood glucose,insulin,lipids,body weight,visceral fat content,histological change of aorta and the expression levels of ICAM-1,MCP-1 and NF-κB/IκBα were determined after the rats were fed for 11 weeks. Results(1)The body weight,ratio of visceral fat content over body weight,blood glucose,insulin,triglyceride,total cholesterol,LDL-C,and total FFA were significantly increased in HF group after 11 weeks feeding compared with control or HF+NAC(all P<0.01);(2) A break in aortic intima integrity,exfoliation of endothelial cell,increase of foam cell number and infiltration of inflammatory cell were observed in HF group,while there were not these changes in both control and HF+NAC groups;(3)A high expression levels of NF-κB,ICAM-1 and MCP-1,and little expression of IκBα were detected in aortic tunica intima in HF group,while little or no expression of NF-κB,ICAM-1 and MCP-1,and a high expression level of IκBα were detected in aortic tunica intima in control and HF+NAC groups.Conclusions High fat-feeding induces macrovascular disease possibly through activation of NF-κB in rat,while antioxidant and NAC effectively prevent the macrovascular diseases in rat fed with high fat.