An optimized process for protein encapsulation was applied to formulate epidermal growth factor (rhEGF)-poly-epsilon-caprolactone microspheres. Microparticles mean size was 3.8 mu m +/- 0.2 and the encapsulation efficiency was 41.9% +/- 2.6. rhEGF recovery after the encapsulation process was similar to 70% (41.9% inside the microspheres and 30% still active in the external phase). In vitro release experiments in McIlvaine buffered solution showed a rhEGF sustained release over 4 days. Skin absorption studies conducted on full-thickness human skin using the Franz cell method showed that 20% rhEGF was released from the microspheres after 24 h exposure. Microspheres accumulated in the stratum corneum where they may act as a rhEGF reservoir. Therefore, rhEGF-PCL microparticles seemed to be promising systems due to their ability to provide locally a sustained release of rhEGF in skin layers.