The aim of this study was to prepare a liposomal delivery system for rapamycin and study its in vitro release characteristics. The results may provide a foundation for the further development of a liposomal delivery system for rapamycin and the establishment of a new active treatment method targeted towards the cellular components of atherosclerotic plaques. The ethanol injection method was used to prepare rapamycin-containing liposomes. The formulation was optimized by orthogonal design, and the degree of rapamycin release by the liposomes was measured by the reverse dialysis method. Orthogonal testing showed that the optimum formulation had a phospholipid concentration of 4%, a phospholipid-cholesterol mass ratio of 8:1, a drug-lipid mass ratio of 1:20 and an aqueous phase pH of 7.4. Rapamycin-containing liposomes with an encapsulation efficiency of 82.11±2.13% were prepared, and the in vitro release of rapamycin from the liposomes complied with a first-order kinetic equation. In conclusion, the formulation was optimized, the prepared liposomes had a high rapamycin encapsulation rate and good reproducibility, and their in vitro release had a certain delayed-release effect.