Aim This study aimed for a detailed understanding of the impact of different process parameters involved during celecoxib-loaded microsphere preparation based on propylene carbonate emulsion-precursors. Methods Microspheres were prepared by a modified emulsification-solvent extraction method. Performed investigations included polymer solubility and viscosity, microsphere size, morphology and stability, propylene carbonate content as well as celecoxib solid state, content and release. Results Rough-walled round microspheres with sizes between 21 mu m and 122 mu m and an internal sponge-like structure filled with residual propylene carbonate (content between 1.9 +/- 0.1% and 6.7 +/- 0.5% w/w) were obtained. Encapsulation efficiencies varied between 28.3 +/- 0.1% and 66.8 +/- 1.0%. The release rates were affected by the polymer concentration, the emulsion phase ratio and the residual propylene carbonate content (t(50%) varied between 2.2 hours and 23.4 hours). Conclusions This study identified the most relevant process parameters for this new preparation method for the model drug celecoxib.