Abstract: Objective To observe the effect of melittin on angiogenesis and discuse the mechanisms. Methods The proliferation, adhesion, migration, tube formation ability of endothelial progenitor cells(EPCs) were detected.Using MTT colorimetric method, adhesion experiment, Transwell cell migration experiment,tube formation experiment,respectively. Through the Western blot method, VEGFR1, VEGFR2, AKT, ERK1/2 phosphorylation expression of EPCs were determined. Results As the role of melittin concentration increases, proliferation of EPCs is stronger inhibited.When melittin concentration is below (including) 2 μg/ml, it does not show obvious cytotoxicity.The 1 and 2 μg/ml concentration groups of Melittin have obvious inhibitory effect on adhesion, migration and tubular formation of EPCs(P﹤0.05) vs. 0 μg/ml group.Melittin can obviously inhibit phosphorylation in EPCs and reduce VEGFR2 expression, but VEGFR1 expression had no obvious change. Conclusion Melittin can obviously inhibit proliferation, adhesion, migration and tube formation of EPCs. Mechanisms may be that Melittin inhibits phosphorylation of signal transduction pathway in EPCs, thereby VEGFR2 protein expression is down-regulated.