In this study, zein microparticles and drug-loaded zein microparticles were prepared using supercritical ASES technique. The effects of operating parameters on particle size and morphology were investigated. ASES-processed zein microparticles consisted of agglomerates of very fine unit particles. As temperature increased, the size of unit particles increased and their morphology became more spherical. The addition of water to the solvents for zein resulted in the formation of more spherical microparticles. The release characteristics of drug-loaded zein microparticles were also studied.