Abstract: Polypeptide from Chlamys farreri (PCF) , as the research object, was embedded in the liposomes, with the encapsulation efficiency as a measure indicator.Three parameters were optimized using central composite design and RSM ( response surface methodology) based on the single factor experiment for achieving maximum encapsulation efficiency of liposomes.Under the condition of pH4 ⁷, the optimum preparation conditions were obtained as follows :phosphatidylcholine 200mg, cholesterol 56mg, Tween 80 68mg, PCF 2.15mg/mL.Under these conditions, the average encapsulation efficiency was 96.05%.The quality was assessed, the liposomes have a fairly good chemical stability and a diameter of below 200nm, carried negative charges.Encapsulation efficiency of PCF liposomes were increased significantly by RSM method and more application developments were achieved.