Abstract: Water soluble drugs carried in liposomes have rather low encapsulation percentage (EP%) and poor stability. In this paper metronidazole (Ⅰ) was chosen as a model of water soluble drugs which was modified by means of esterification. Its myristic ester (Ⅱ) was synthesized. On studying the liposomes of Ⅰ and Ⅱ, the results have shown that EP% and stability of Ⅱ were more than ten times as high as that of Ⅰ. Furthermore, the reconstitutable liposomes of Ⅱ were prepared successfully. The amoebacide activity of Ⅱ liposomes was increased also. Therefore, the hydrophobic modification of water soluble drugs is a good way to improve the drug entrapped in liposomes.