Objective: To study the effect of Endothelin-1 (ET-1) on cell proliferation in primary cultures of human dental pulp cells; the cell mechanism of mitogen; and collagen synthesis. Methods: Primary cultures of human dental pulp cells; Thiazolyl Blue Tetrazolium Bromide (MTT) test to investigate cell proliferation; measurement of calcium ions in human dental pulp cells with the calcium-sensitive dye fluro-3; enzyme-linked immunosorbent assay and avidin-biotin complex immunocytochemical assay for collagen synthesis in human dental pulp cells. Results: Incubation of cultures with ET-1 resulted in a dose-dependent increase in cell proliferation over control (unstimulated) cultures. In addition ET-1 increased the Ca2+ concentration in human dental pulp cells, which cannot be inhabited by Verapamil. The finding demonstrated that collagen type I synthesis of human dental pulp cells was increased by ET-1. Conclusions: ET-1 played a crucial role in pulp restoration of lesions and had an effect on mitogen and differentiation of human dental pulp cells.