Vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF) are well known angiogenesis inductors and promoters in normal and pathologic conditions. Recent data showed that VEGF-A and HGF could also influence lymphangiogenesis but this matter has not been completely elucidated. Administration of VEGF-A and HGF in combination has been used to improve the angiogenic response in different experimental models, but their effects on lymphangiogenesis have not been investigated. The aim of this study was to characterize blood and lymphatic vascular response to VEGF-A/HGF administration. To this purpose, we built a pBlast VEGF-A/HGF combination suitable for in vivo research. By using as an experimental in vivo model the chick embryo chorioallantoic membrane (CAM) assay, we applied pBlast VEGF-A/HGF combination for 7 days. Results showed that VEGF-A/HGF combination was able to induce a strong angiogenic response and the expression of Prox-1 in the lymphatic endothelial cells of the CAM. The possible mechanisms involved have been speculated.