Objective: The development of three-dimensional (3D) biomaterial scaffold with surface properties in combining with mesenchymal STEM CELL (MSC) provide desirable alternative for bionanomaterial–CELL transplantation therapy of neurodegenerative. In this regard, we investigated the potential of rat bone marrow derived Mesenchymal STEM CELLs (MSCs) for neuronal differentiation in vitro on poly- (e-caprolactone) nanofibrous scaffolds.Materials and Methods: PCL nanofibrous scaffolds were fabricated by electrospinning process and surface modified by a simple plasma treatment process for enhancing the Mesenchymal CELL adhesion, proliferation and interactions with nanofibers necessary for nerve tissue formation. Then the chemical and mechanical characterizations of nanofiber were carried out using SEM, contact angle and tensile instrument. The differentiation of MSCs was carried out using neuronal inducing factors including basic fibroblast growth factor, nerve growth factor and brain derived growth factor in DMEM/F12 media. The expression of neural protein markers was analyzed by immunocytochemistry.Results: Scanning electron microscopy results showed normal morphology of Mesenchymal CELL on PCL nanofiber scsffold. The differentiated Mesenchymal CELLs on nanofiber scaffold were found to express the neuronal proteins, b- tubulin III and Map2 on day 15 after culture.Conclusion: Our studies on the differentiation of MSCs to neuronal CELLs on nanofibrous scaffolds suggest their potential application towards nerve regeneration.