Parkinson's is a major neurodegenerative disorder that occurs due to loss of dopaminergic neurons in basal ganglia. Conventional therapy includes surgery that involves lot of risk and administration of levodopa which is accompanied by poor bioavailability, short half-life, and side effects. In the present study, poly(butylene succinate) (PBSu) microspheres-based drug delivery system to improve the bioavailability of the drug levodopa was evaluated for the first time. Biodegradable porous and smooth PBSu microspheres were prepared by double emulsion solvent evaporation technique (W/O/W) and the effect of solvent and surfactant was studied. The maximum encapsulation efficiency achieved was 53.93% and 62.28% for porous and smooth microspheres, respectively. In vitro drug release was studied in phosphate buffered saline and simulated CSF buffer of pH 7.4. Initially a burst effect followed by sustained release of drug was obtained for about 32 h and 159 h for porous and smooth microspheres, respectively. The release rate was higher in simulated CSF when compared with PBS, due to higher concentration of sodium ions and cations in simulated CSF. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.