In our efforts aimed at studying the cellular responses to injury, including the angiogenesis of wound healing, we have developed a novel three-dimensional (3D) skin equivalent that is comprised of multiple cell types found in normal human skin or chronic wound beds. Thein vitromodel contains a microvascular component within the dermis-like extracellular matrix and possesses an intact epithelial covering comprised of skin-derived epithelial cells. Capillary endothelial cells can be labeled with fluorescent vital tracers prior to being embedded within a 3D matrix and overlaid with a monolayer of keratinocytes (normal or transformed). Once embedded in the matrix, the endothelial cells demonstrate capillary-like tube formation mimicking the microvasculature of true skin. Angiogenesis and the reepithelialization, which occur in response to injury and during wound healing, can be quantified using fluorescence-based and bright-field digital imaging microscopic, biochemical, or molecular approaches.