Water-insoluble genistein was solubilized in aqueous medium by using phospholipid vesicles composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycerophosphocholine (DOPC) with 0-30% cholesterol. For each vesicle, the maximum solubilization amount of genistein was investigated by X-ray scattering measurement. In addition, the antioxidant capacity of the solubilized genistein was evaluated by the ABTS assay. Genistein was found to be solubilized by 10-20% and 40-50% of the vesicle concentrations of pure DPPC and DOPC respectively. The maximum solubilization amount of genistein decreased to 0-10% and 20-30% when 30% of cholesterol is present in the respective vesicles. Cholesterol is solubilized in a hydrophobic core whereas genistein is solubilized in the polar head region or in the polar-apolar interface. The overlapping of solubilizing sites affected the solubilization of genistein when cholesterol was present in the vesicles. Moreover, the lamellar interval was largely affected by cholesterol in compared to the little impact of genistein because the later can indirectly affect the acyl chains. Genistein solubilized in DOPC showed the same degree of antioxidant capacity as that of vesicle-free genistein system. On the other hand, genistein solubilized in DPPC had lower antioxidant activity than the former systems. The distinction of antioxidant activity at different systems probably related to the difference of accessibility of ABTS radical cation to solubilized genistein through different vesicles. Finally, cholesterol-free DOPC vesicles were found to be the best solubilizer for genistein among the investigated systems.