Objective：To investigate the relationship of plasma protein levels of epidermal fatty acid binding protein（E-FABP） and fatty acid synthase（FASN） with risk factors of human femoral atherosclerosis. Methods：One hundred and seventy-eight patients were detected by color Doppler with intimal-media thickness（IMT） measurement. Then，patients were divided into femoral atherosclerosis group（n=128） and control group（n=50） according to IMT. Fasting protein levels of E-FABP and FASN in plasma were detected and their relationship with femoral atherosclerotic risk factors was measured. Results：Plasma protein levels of E-FABP and FASN in atherosclerotic group were increased compared with those in control group（P<0.05）. Correlation analysis showed that there was a pos－itive correlation between plasma levels of E-FABP and FASN（P<0.05）. E-FABP level was correlated positively with age，body mass index（BMI），triglyceride（TG），adiponection，C reactive protein（CRP） and IMT（P<0.05）. FASN level was correlated positively with age，BMI，fasting plasma glucose，homeostasis model assessment-insulin resistance（HOMA-IR），TG，adiponectin，CRP and IMT（P<0.05）. Plasma levels of E-FABP and FASN were negatively correlated with high-density lipoprotein-cholesterol（P<0.05）. Logistic re－gression analysis showed that age，FASN，E-FABP，HOMA-IR，CRP and TG were the risk factors of femoral atherosclerosis（P<0.05）. Conclusions：Femoral atherosclerosis associated with plasma levels of E-FABP and FASN，which maybe a new circulating biomarker in diagnosis and evaluation of human femoral atherosclerosis.