Biodegradable amphiphilic graft copolymers with different compositions were synthesized by grafting poly(L-lactide) (PLLA) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The critical micelle concentration (CMC) of the graft polymers was determined by fluorescence probe technique. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the graft polymers were proved to have low cytotoxicity. Based on the specific physicochemical property of the graft copolymers, submicron sized microsphere drug delivery systems were prepared by a very convenient "ultrasonic dispersion method", which did not involve toxic organic solvents. The drug-loaded microspheres had a regular spherical shape with a narrow size distribution. A hydrophobic drug, prednisone acetate, was encapsulated into polymeric microspheres and the in vitro drug release was studied.