Objective: To optimzie preparation process of pomegranate peel polyphenols liposomes by using supercritical CO2 fluid precipitation technology. Method: With entrapment efficiency as index,main factors were screened by Plackett-Burman test,preparation process of pomegranate peel polyphenols liposomes was optimized by steepest ascent test and Box-Behnken test. Result: Ratio of raw materials and membrane material,reaction temperature and pressure were significant factors,optimal preparation conditions was as following:ratio of raw materials and membrane material of 1: 21.15,reaction temperature at 48.3 ℃,reaction pressure of 23.88 MPa.The measured value and the predicted value of entrapment efficiency were 80.295% and 81.379%,effective size was 168.5 nm,Zeta potential was -73.8 mV. Conclusion: This test model meets requirements.In vitro release of pomegranate peel polyphenols liposomes is slow,its sustained release effect is obvious.