Aim To explore the effect of enhanced external counterpulsation (EECP) against atherosclerosis and its endothelial mechanisms. Methods Twelve hypercholesterolemic pigs were randomly divided into the hyperlipidemia and EECP groups. After EECP,amount to 36 hours,the coronary arteries and abdominal aortas were sampled for histopathologic and ultrastructural examination. The endothelial cells (EC) were collected from thoracic aorta for proteomic study. Results Compared with the hypercholesterolemic animal receiving EECP,much more plaques were found in the hypercholesterolemic animal without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP (1.27%±0.35%) versus (7.83%±2.39%) in those without EECP,P<0.05. Lipid deposition,endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those without EECP. Moreover,eight kinds of proteins were higher expressed in ECs from animals receiving EECP than from those without EECP. Conclusion EECP could prevent atherosclerotic lesion progress by repairing damaged endothelia caused by hypercholesterolemia.