The aim of this study was to develop a microparticulate delivery system for acid-labile lansoprazole. The solvent evaporation method was employed to prepare Eudragit® RS-100 microparticles (RS-microparticles). The effects of three parameters, including polymer concentration, drug concentration and homogenization rate, on microparticle performance were evaluated. The results revealed that the homogenization rate played an important role on the microparticle size. Increasing the polymer concentration and decreasing the drug concentration enhanced the efficiency of drug encapsulation in RS-microparicles. The release of drug from RS-microparticles was governed by both Fickian diffusion and polymer swelling mechanisms. The RS-microparticles were further enteric coated by hydroxypropyl methyl cellulose phthalate (HPMCP) to improve the acid-resistance of lansoprazole.