Microspheres containing bovine serum albumin (BSA, a model drug) were prepared via double emulsion solvent evaporation using the compound of poly(3-hydroxybutyrate) (PHB) and polyethylene glycol (PEG) as the matrix. Influences of introduction of BSA and wall polymer composition on BSA-PHB/PEG microspheres characteristics were studied by means of DSC, XRD, optical microscope (OM), SEM, FTIR, etc. The crystallinity of PHB dropped when PEG was brought in the compound, and it decreased with the increasing proportion of PEG. BSA-PHB/PEG microspheres had still lower crystallinity than PHB/PEG compound and raw materials. The yield and protein loading of the microspheres reached 36.1% and 12.2%, respectively, at the optimum mass ratio, m(PHB) : m(PEG) = 4/1. FTIR results confirmed the existence of BSA in the microspheres and revealed the absence of chemical interaction between BSA and polymers. It was found that the mass ratio of PHB to PEG had direct effect on the size distribution, surface morphologies, and microstructure of microspheres. The mean particle size of microspheres ranged between 2.9 and 5.0 mu m measured by optical microscopy, depending on the different proportion of PEG. The results from the OM observations combined with SEM micrographs showed that PHB/PEG microspheres were likely to have porous surface and a structure of microspheres embeded. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media, and the result indicated that the BSA-PHB/PEG microspheres had a quicker release rate and a higher accumulative release amount than BSA-PHB microspheres, which showed the feasibility and superiority of BSA-PHB/PEG microspheres as controlled release devices. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 114: 818-825, 2009