Angiogenesis play a crucial role in the regeneration of hard and soft tissue around dental titanium (Ti) implant. Enamel matrix derivative (EMD) promotes tissue regeneration and stimulates angiogenesis but its effect on the angiogenesis on Ti surfaces was never investigated. The effect of EMD on the angiogenic activity of endothelial cells cultured on pre-treated smooth Ti (PT), acid etched (A), coarse -grit blasted and acid-etched (SLA) surfaces and tissue culture plastic (TCP) in the presence or absence of EMD was investigated. EMD inhibited the proliferation/viability of human umbilical vein endothelial cells (HUVECs) growing on A and SLA Ti surfaces. EMD induced an increase in the expression of all these genes in HUVECs grown on SLA surface but not on other surfaces. Summarizing, our data show that EMD influences proliferation and expression of angiogenesis associated gene in HUVECs grown on moderately rough SLA surfaces, suggesting that EMD might promote angiogenesis following implantation.