The present study describes the development of a new cyclosporine formulation based on polycaprolactone (PCL) microspheres (MS) prepared by the solvent evaporation method. Ternary phase diagrams were used to identify the domains where MS were formed. The application of central composite designs established the influence of several technological (stirring speed) and formulation factors (polymer and surfactant amounts, and organic solvent volume) on the size of PCL MS. Cyclosporine-loaded MS of a size around 2.5 #181;m were prepared and characterized. The stability of the systems, either alone or loaded with cyclosporine, stored at 8#176;C and room temperature (RT) was assessed as well. Freeze-drying was evaluated as an alternative method to achieve longterm stability. The experimental design showed that the stirring speed and the organic phase volume were the only parameters significantly affecting the MS size. Experimental conditions selected to obtain CyA-loaded MS of 2.5 #181;m resulted in a high entrapment percentage (98.4 - 0.66%), with the drug dissolved or molecularly dispersed within the dense polymeric matrix of MS. After 12 months of storage at 8#176;C and RT, PCL MS remained physically stable, although the crystallinity of the polymer increased by 35% upon storage at both temperatures. Freeze-drying studies revealed that MS could be successfully lyophilized in the absence of cryoprotectants without significant changes of the drug entrapment; however, the presence of at least 5% cryoprotectant was essential to keep the initial particle size. Therefore, a stable MS-based CyA formulation was easily prepared and characterized. This formulation offer the possibility of CyA administration through different routes.