Floating acrylic resin microspheres with an internal hollow structure were prepared by a solvent diffusion and evaporation method. The yield of microspheres depended on the diffusion rate of ethanol and/or isopropanol in the organic phase. They were successfully produced when a mixture of ethanol and isopropanol was used instead of ethanol alone. The mixing ratio of components in the organic phase affected the size and the yield of microspheres and the best results were obtained at the volume ratio of ethanol:isopropanol:dichloromethane (8:2:5). Direct introduction of the organic phase into the aqueous phase through a glass tube also significantly improved the yield by avoiding the contact of organic phase with the surface of water. The optimum rotation speed and temperature were 250 rpm and 25 degrees C, respectively. Several different drugs with various physico-chemical properties were used as model drugs for encapsulation and release tests. When a drug had low solubility in dichloromethane and high solubility in both water and a mixture of ethanol/isopropanol, the loading efficiency was the lowest. The release profiles were significantly different depending on the solubility of a drug in the release medium and the physico-chemical properties of an encapsulated drug.