Neural progenitor cells have shown the effectiveness in the treatment of Parkinson's disease, but the therapeutic efficacy remains variable. One of important factors that determine the efficacy is the necessity of pre-differentiation of progenitor cells into dopaminergic neuronsbefore transplantation. This study therefore investigated the therapeutic efficacy of mesencephalon-derived human neural progenitor cellswith or without the pre-differentiation in alleviating a rat model of Parkinson's disease.We found that a combination of 50ng/ml fibroblastgrowth factor 8, 10ng/ml glial cell line-derived neurotrophic factor and 10M forskolin facilitated the differentiation of human fetalmesencephalic progenitor cells into dopaminergic neurons in vitro. More importantly, after transplanted into the striatum of parkinsonianrats, only pre-differentiated grafts resulted in an elevated production of dopamine in the transplanted site and the amelioration of behavioralimpairments of the parkinsonian rats. Unlike pre-differentiated progenitors, grafted intact progenitors rarely differentiated into dopaminergicneurons in vivo and emigrated actively away from the transplanted site.These data demonstrates the importance of pre-differentiation of human progenitor cells before transplantation in enhancing therapeuticpotency for Parkinson's disease.