We prepared the sirolimus liposome by rapid expansion of supercritical solution (RESS) technology of supercritical fluid, and studied the effects of temperature, pressure, and equilibrium time on the average particle size and envelop rate of liposome. The conditions of the minimal average particle size of liposome were 328K of temperature (35MPa), 35MPa of pressure (333K), and 50 minutes of equilibrium (343K) time, respectively. The conditions of the maximal envelop rate of liposome were 333K of temperature (30MPa), 35MPa of pressure (343K), and 50 minutes of equilibrium (323K) time, respectively.