To prepare niosomes which have high encapsulation capacity for soluble drugs, starting from Span 60 and cholesterol, an improved method, evaporation-sonication method, was proposed. The corresponding niosomes show a good stability at least 40 days. Colchicine was chosen as a model drug for examining the capsulation capacity of these niosomes. To obtain the highest encapsulation efficiency, several factors including the structure of surfactant, level of lipid, content of drug and cholesterol were investigated and optimized. The inner cause was also discussed. The results indicate that the Span 60 is the most ideal surfactant among four kinds of Span. Furthermore, the release studies of colchicine and 5-fluorouracil (5-FU) in vitro from niosomes exhibited a prolonged release profile as studied over a period of 24 h. The results demonstrated that niosomes prepared in this way not only have high encapsulation capacity but also is expected that side effects of drugs may be reduced. It still suggests that this method may be used extensively in the field of encapsulation soluble drugs.