The polycaprolactone (PCL) microparticles fabricated by electrospray technique have been studied and applied in drug and protein delivery system. The degradation of PCL and the release of drug/protein from the polymeric microparticles (MPs) were desired to happen simultaneously. When the new dosage was administrated, the PCL MPs were degraded and eliminated out of the body. This research indicated that the degradation of PCL was influenced by the various morphology of electrosprayed microparticles. The different sizes of 11.8 μm and 5.17 μm and the various shapes of the PCL MPs such as hollow, porous and wrinkle particles and spheres were investigated the PCL degradation in the PBS solution, at pH 7.4. The morphology of PCL MPs was designed by controlling the polymer solution and the electrosprayed processing parameters such as the flow rate and collecting distance. Scanning electron microscopy and gel permeation chromatography were order to determine the change of the morphology and number molecule weight (Mn) of PCL MPs. The porous, distorted and smaller particles reduced the Mn faster than the microspheres because of the larger surface area of MPs contacted with PBS solution. After 77 days, PCL MPs which were fabricated by the processing parameter, including 2.5% PCL in DCM, flow rate of 0.8 mL/h, voltage of 18 kV, collecting distance of 25 cm, reduced 49.96% molecular weight (decreasing from Mn= 80,438 g/mol to 40,225 g/mol).