Objective:To prepare three kinds of liposomes with different solvent medium named common liposomes, ethanol liposomes and propylene glycol liposomes,screen and optimize the preparation process,and investigate the stability preliminarily. Methods:Common liposomes were prepared by a thin film dispersion method, and ethanol liposomes and propylene glycol liposomes were prepared by an injection method. With the same formula compositions,the size distribution of common liposomes was studied with hydration time, water bath temperature and rotation speed. The size distribution of ethanol liposomes and propylene glycol liposomes was studied different volume ratio of alcohol to water, stirring speed and mode of membrane passmg. An orthogonal design was adopted to obtain the optimal preparation technology based on the influences. Preliminary stability of the three different solvent medium liposomes was evaluated respectively on 0,1st,15th and 30th day using the changes of morphology and the mean particle size as the indicators. Results:The results of orthogonal test showed that the best preparation method for common liposomes was as follows:the hydration time was 60 min,the water bath temperature was 50℃ and the rotation speed was 200 r·min-1. The best preparation method for ethanol liposomes and propylene glycol liposomes was as follows:the volume ratio of alcohol to water was 1:2,the stirring speed was 1 000 r·min-1and the mode of membrane passing was 0.45 μm at first and then changed to 0.22 μm. Under the optimum preparation conditions, the three liposomes were closed monolayer or multilayer cystic spherosomes. The average diameter of common liposomes, ethanol liposomes and propylene glycol liposome was (1 016.2 ± 135.6),(578.7 ± 89.2) and (351.4 ± 53.8) nm, respectively. All the three liposomes were unstable during the one-month observation period. After the 15-day storage, obvious delamination appeared.Conclusion:Three different solvent medium liposomes prepared with the best process are in micro-scale or nano-scale. They are in poor stability, which should be freshly prepared before use.