Biodegradable microspheres containing salbutamol sulphate were prepared using water-in-oil-in-water (w/o/w) emulsion technique. Biodegradable polymers of two different molecular weights were used: PLGA 50/50 and PLGA 75/25. In the preparation of the formulations, we used 2(3) factorial design based on three independent variables which are drug loading, amount of gelatin and concentration of PVA. The dependent variables are particle size of the microspheres and entrapment ratio %. The in-vitro release of PLGA microspheres was studied in buffer solution of pH 7.4 at 37 degrees C. a biphasic release behavior of salbutamol sulphate from microspheres was observed. Initially, a burst effect and then slow release was observed. It was found that the biodegradable microspheres of salbutamol sulphate were prepared with PLGA 75/25 by w/o/w emulsion technique obtained extended release obtained for 8 h. PVA concentration was effective on the particle size of microspheres prepared with PLGA 75/25 (p < 0.05).