Abstract： Objective To explore the effect of enhanced external counterpulsation (EECP) on platelet membrane fluidity and lipid peroxidation in hypercholesterolemic pigs, and to investigate the mechanisms by which EECP acts against artherosclerosis. Methods Eighteen male infant pigs were randomly divided into 3 groups according to their diet: the normal diet control group (n=6) , the hypercholesterolemia control group (n=6) and the hypercholesterolemia + EECP group (n=6). After porcine hypercholesterolemia model was established in the latter two groups, EECP was given to the hypercholesterolemia+EECP group by 2 h per session, once every two days, for up to 36 h. Blood samples were collected from all the animals to measure the levels of total cholesterol (Chol), low density lipoprotein (LDL) and lipid peroxidation before hypercholesterolemia modeling, prior to EECP treatment, during the EECP treatment (on day 18) and after completion of EECP treatment (on day 36). In addition, platelet membrane fluidity as reflected by fluorescence polarizability (P') was measured according to Caimi's methods. Results The levels of Chol and LDL were significantly higher in hypercholesterolemic pigs with or without EECP treatment compared with normal diet control group before, during and after EECP (all P＜0.05), whereas there were no significant differences in P' and lipid peroxidation among 3 groups before allocation to different diets (P＞0.05). The fluorescence polarizability P' and level of lipid peroxidation were remarkably elevated in both hypercholesterolemia control group and the hypercholesterolemia+EECP group before, during and after EECP compared with the normal diet control group at the same time points (all P＜0.05) , and were remarkably lowered in the hypercholesterolemia + EECP group compared with hypercholesterolemia control group during and after EECP[P':(0.451 ±0.047)vs(0.655±0.034), (0.561±0.043) vs (0.723±0.050) ;lipid peroxidation: (0.56±0.06)mmol/L vs (0.88±0.07)mmol/L, (0.72±0.13)mmol/L vs( 1.23±0.11 )mmol/L, all P＜0.05]. Conclusion EECP may lead to reduced lipid peroxidation and improve platelet membrane fluidity, and thereby delay the pathophysiological progression of hypercholesterolemia, which might be one of mechanisms of its anti-atherosclerotic effect.