Urotensin-II (UII), along its receptor UT-R, is widely expressed in the cardiovascular system, where it exerts regulatory actions under both physiological and pathological conditions. Real-time PCR and immunocytochemistry demonstrated the expression of UII and UT-R as mRNA and protein in rat neuromicrovascular endothelial cells (NECs). UII did not affect the proliferation rate of cultured NECs, but exerted a strong angiogenic action in both an in vitro assay on Matrigel and an in vivo assay on chorioallantoic membrane. The angiogenic effect of UII was similar to that of FGF-2, and was abolished by the UT-R antagonist Palosuran. Collectively, our findings allow us to include UII in the group of cytokines (e.g. endothelin-1 and adrenomedullin), which are expressed in endothelial cells and exert a pro-angiogenic effect acting in an autocrine-paracrine manner.