To investigate the research of the tumor seeker using liposomes with negatively stained. The fine structure and size in liposomes composed of PC, DSPC, DAPC and SM phospholipid were observed. And the yield of vesicle affected with sonication by mechanical force were determined. The results were as follows. 1. The stain of 2% UA are obtained a good resolution from electron microscopic observation to compare the negatively liposomes with PTA, AM and UA solution. 2. The fine structure of liposomes except DAPC, PC and CH alone samples could be observed from EM experiment of liposomes composed of PC, DSPC, DAPC and SM phospholipid. 3. The results of experiment from 10, 20, 40 and 60 times sonication with 30sec, prepared 0.1mM NTA-SM-liposomes were obtained unilamella vesicles from groups of multilamella vesicles of phospholipid. 4. About 50nm diameter liposomes obtained through membration filtration step to prepare homogenized liposomes.