Abstract: Clinical performance of currently available human skin equivalents is limited by failure to develop perfusion. To address this problem we have developed a method of endothelial cell transplantation that promotes vascularization of human skin equivalents in vivo. Living skin equivalents were constructed by sequentially seeding the apical and basal surfaces of acellular dermis with cultured human keratinocytes and Bcl-2 transduced HUVEC or umbilical cord cells sequentially. After orthotopic implantation of grafts comprising cultured human keratinocytes and Bcl-2 transduced HUVEC cells onto mice, the grafts displayed both a differentiated human epidermis and perfusion through the HUVEC-lined microvessels. These vessels, which showed evidence of progressive maturation, accelerated the rate of graft vascularization. Successful transplantation of such vascularized human skin equivalents should enhance clinical utility, especially in recipients with impaired angiogenesis.