The secreted vascular endothelial growth factor-D (VEGF-D) induces the growth of blood and lymphatic vessels, promotes solid tumor growth, distant organ metastasis, and its expression is correlated with poor patient outcome. VEGF-D is therefore considered a potential target for novel anti-cancer therapeutics designed to restrict the growth and metastatic spread of cancer. In order to model the effects of systemically targeting human VEGF-D for therapeutic purposes, and to explore the biological function of this protein, we previously generated a Vegfd knockout mouse by homologous recombination. The Vegfd knockout mice, on a mixed genetic background, were healthy and fertile, indicating that mouse Vegf-d is dispensible for development of the lymphatic and blood vascular systems. Here, we analyse the characteristics of the lymphatic network in Vegfd knockout mice on a pure genetic background, and report altered lymphatics and blood vessels in the skin of these mice compared to littermate controls. Further, we explore the functional implication of this vascular phenotype by analysing the angiogenesis and lymphangiogenesis that occur after challenging the skin of these mice with cutaneous wound healing. Our studies reveal that the healing process is altered in Vegfd knockout mice, in comparison to wild-type controls, with differences in the formation of blood vessels and lymphatics and in the rate of wound closure. Delivery of mouse Vegf-d to adult tissue further confirmed that this protein modulates the patterning of blood vessels and lymphatics in adult skin. These findings demonstrate that Vegf-d plays a role in adult tissue remodelling and indicate that therapeutic approaches targeting VEGF-D in cancer should consider the potential effects on wound healing, particularly in relation to cancer surgery.