A series of biodegradable PEG-containing polyanhydrides composed of sebacic acid, 1, 6-bis(p-carboxyphenoxy) hexane, and poly (ethylene glycol) (PEG) were used as matrix material for BSA-loaded microspheres. The effects of polymer composition on the microsphere size, entrapment efficiency, in vitro degradation, and in vitro protein release were studied. Microspheres in the size range of 0.8-10 mu m were fabricated via a modified double emulsion method and were characterized using scanning electron microscopy. As the content or the molecular weight of PEG was increased in the copolymer, a proportional increase was found in the particle size and the efficiency of BSA could be controlled by varying the polymer composition, increasing as the PEG proportion increased. In vitro release studies of BSA from polyanhydride microspheres revealed that the increased amounts of PEG within microspheres could accelerate the release rate of protein. These studies indicate that the PEG-containing polyanhydrides hold potential for protein delivery applications. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 352-358, 2011