The aim of this study was to develop ethylcellulose microspheres for prolonged drug delivery with reduced burst effect. Ethylcellulose microspheres loaded with ibuprofen were prepared with and without polystyrene, which was used to retard drug release from ethylcellulose microspheres. Ibuprofen-loaded ethylcellulose microspheres with a polystyrene content of 0-25% were prepared by the solvent evaporation technique and characterized by drug loading, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. The in vitro release studies were performed to study the influence of polystyrene on ibuprofen release from ethylcellulose microspheres. The microspheres showed 28-46% of drug loading and 80-92% of entrapment, depending on polymer/drug ratio. The infrared spectrum and thermogram showed stable character of ibuprofen in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 0.1-4 microm. Ethylcellulose/polystyrene microspheres showed prolonged drug release and less burst effect when compared to microspheres prepared with ethylcellulose alone. Microspheres prepared with an ethylcellulose/polystyrene ratio of 80:20 gave a required release pattern for oral drug delivery. The presence of polystyrene above this ratio gave release over 24 h. To find out the mechanism of drug release from ethylcellulose/polystyrene microspheres, the data obtained from in vitro release were fitted in various kinetic models. High correlation was obtained in Higuchi and Korsmeyer-Peppas models. The drug release from ethylcellulose/polystyrene microspheres was found to be diffusion controlled.