UVA1-mediated effects regarding vascular dysregulation as a primary pathogenetic factor of systemic sclerosis skin lesions have so far not been investigated. Pre- and posttherapy skin biopsies of four patients were evaluated immunohistochemically for angiostatic, angiogenic and angioapoptotic features. Immunohistochemistry revealed a partial pretherapy loss of endothelial CD31 and CD34 expression accompanied by a posttherapy increase of CD34(+) cells. Simultaneously, VEGF and M30 CytoDEATH immunolabeling demonstrated UVA1-induced neovascularization and decreased endothelial apoptosis. Our results suggest that UVA1 irradiation exerts its positive effects by a modulation of endothelial regulation/transformation beside the proposed induction of T cell apoptosis and collagenases.