Tumor vasculatures generated by tumor angiogenesis are different from normal vasculatures in the morphology and function. These distinct features of tumor vessels are, in part, caused by transcriptional changes in endothelial cells during tumor angiogenesis. To understand the transcriptional regulation in endothelial cells during tumor angiogenesis, we have studied the expression and role of transcription factor Sox17 in tumor endothelial cells by using loss-of-function and gain-of-function genetic mouse models as well as a reporter mouse system. Sox17 was highly expressed in almost all tumor endothelial cells during the whole tumor angiogenesis. Its expression in tumor endothelial cells showed a strong correlation with sprouting angiogenesis. Indeed, Sox17 promoted tumor angiogenesis by sprouting. Sox17 also modulated the shape and function of tumor vessels by regulating vascular integrity in endothelium and periendothelial compartment. These vascular changes by Sox17 resulted in many changes of tumoral responses. We currently pursue to elucidate the cellular and molecular events led by Sox17 in tumor endothelial cells. Our studies demonstrate endothelial Sox17 as a key player for angiogenesis and the morphogenesis of tumor vessels by regulating gene expression.