Aim To investigate the influence of transforming growth factor-α （TGF-α） on the differentiation capacity of human endothelial progenitor cells（EPC） and to explore its mechanism of action. Methods EPC were isolated from peripheral blood of healthy people, and cultured with complete medium containing 0, 1, 10 μg/L concentration of TGF-α. Morphological changes were observed in each group in EPC differentiation. By using the flow cytometry, the CD34⁺/CD133⁺ and CD31⁺/vWF⁺ positive cells were detected during the differentiation of cultured EPC with TGF-α. The expression of eNOS and Flk-1/KDR genes, the specific genes of EPC differentiated endothelial cells, were determinated by Real-time PCR. The NO content changes in each group were detected. The TGF-α receptor （EGFR） and vascular endothelial growth factor （VEGF） expression in EPC differentiation were tested by Western Blot. Results The cell morphology of EPC induced and cultured by TGF-α, could faster differentiate stem cells from the spherical to spindle cells.