The molecular mechanisms initiating the formation of the lymphatic system， lymphangiogenesis， are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor， Etv2/Etsrp， a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1 day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis， while development of blood vessels is unaffected. In Etv2-inhibited embryos and larvae， the number of lymphatic progenitors is greatly reduced， the major lymphatic vessel， the thoracic duct， is absent or severely fragmented， and lymphangiogenesis-associated marker expression， including lyve1b， prox1a， and vegfr3/flt4， is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1， and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein.