Abstract: Objective In order to investigate the effect of Desert Hedgehog on direct differentiation of neural progenitor cells (NPCs) cultured from embryonic mesencephalon in the rats. Methods We infected DHH into COS7, NIH/3T3 and 9L cells, and detected the expression of DHH in the cells with immunofluorescence, Real- Time PCR and Western blot. All of the three cells were co-cultured with the NPCs isolated from the ventral mesencephalon in embryonic SD rats (E13.5), respectively. The detection of immunoreactivities of tyrosine hydroxylase (TH) was made by immunocytochemistry after 10 days in vitro. Result The expression of DHH in COS7, NIH/3T3 and 9L cells was remarkably detected, but little TH-positive cells could be found in the three co-cultral systems at the 10th day. Conclusion The protein derived of DHH itself does not show any inductive impact on.the differentiation of NPCs to the dopaminergic neurons in vitro.