Aim To discuss the relationship between vascular endothelial cell injury, changes of serum endogenous metabolites and pathogenesis of arteriosclerosis obliterans （ASO）. Methods ASO models were constructed with the method of high-fat diet plus intimal injury. At 8 weeks after operation, the arterial morphology was observed using light microscopy, the number of circulating endothelial cells （CEC） was determined using percoll density gradient centrifugation method, serum endothelin-1 （ET-1） and nitric oxide （NO） levels were detected using ELISA double antibody sandwich assay, changes of endogenous metabolites in serum were analyzed with the metabonomics method-based gas chromatography-mass spectrometry （GC/MS） technology. Results Rat models of ASO were established successfully, the number of CEC in ASO rat peripheral blood increased significantly, the serum ET-1 level was significantly higher, and the level of NO was significantly less than normal control rats after operation （P<0.01）. Compared to normal control group, metabolism of the sugars, amino acids, fatty acids in serum of ASO rats were significantly changed. Conclusions Vascular endothelial cell injury and changes of serum endogenous metabolites mediated ASO, protecting the vascular endothelial function and adjusting the balance of the endogenous metabolites should be important therapeutic targets of ASO.