Mesenchymal stem cells constitute an potential cellular source to promote brain regeneration with Parkinson's disease. Mesenchymal stem cells have significant advantages over other stem cell types and greater potential for immediate clinical application. The purpose of this study was to investigate whether hMSCs from the human adipose tissue could be induced to differentiate into dopaminergic cells and to assess the developmental potential of hMSC for selectively replacing the midbrain dopamine neurons lost in Parkinson's disease in vitro and in vivo. MSCs were cultured under conditions that promote differentiation of dopaminergic neuron. Using media that include SHH, FGF8, and GDNF. the MSCs were induced in vitro to become dopaminergic neurons. The expressions of the LIM homeobox transcription factor 1, alpha (Lmx1a), tyrosine hydroxylase(TH) proteins were determined by immunofluorescence. Lmx1a has been shown sufficient to confer neurogenic activity on mesencephalic floor plate cells and to determine a mesencephalic dopaminergic neurons fate. This result suggests that hMSCs have the ability to differfentiate into dopaminergic neurons. hMSCs were then transplanted into the striatal in a rat model of Parkinson's disease. The rats were unilaterally lesioned in the substantia nigra with 6-hydroxydopamine and were tested for rotational apomorphine-induced behavior. Following differentiation of dopaminergic neuron, cells displayed dopaminergic morphology and that they expressed dopaminergic marks genes. Finally transplantation of hMSCs into the striatal of Parkinsonian rats resulted in improvement of their behavioral deficits by apomorphine-induced rotational behavior. The hMSCs transplanted rats were proved to be better than compared with the transplantation of PBS. Immunohistochemical analysis of grafted brains revealed that abundant hMSCs survived from the grafts and some of them displayed dopaminergic marks. Our results indicate that hMSC may serve as a good cell source for the treatment of neurodegenerative diseases and have high potential for being used in multiple applications. This cellular approach might become a restorative therapy in Parkinson's disease.