Transforming growth factor-beta 1 (TGF-β1) plays important roles in the endothelial-to-mesenchymal transition (EndMT). Recently, long noncoding RNAs (lncRNAs) have been identified to be involved in the physiological and pathological processes of human diseases. However, the role of endothelial lncRNAs in the TGF-β1-mediated control of angiogenesis and its underlying mechanism remains largely unclear. In this study, we first demonstrated that TGF-β1 induced EndMT; promoted cell viability, proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Second, our study displayed that TGF-β1 upregulated the lncRNA UCA1 expression in HUVECs, knocked down UCA1 with small interfering RNAs, and inhibited the function of TGF-β1 in HUVECs. Third, our study showed that UCA1 was located in the cytoplasm and absorbed miR-455 in TGF-β1-treated HUVECs. Further, the miR-455 inhibitor restored the role of the inhibited UCA1 in HUVECs treated with TGF-β1. Fourth, our study revealed that miR-455 inhibited ZEB1 expression, and overexpression of ZEB1 restored the role of miR-455 in HUVECs treated with TGF-β1. Finally, our study revealed that UCA1 exerted its role via regulating the UCA1/miR-455/ZEB1 regulatory axis in HUVECs treated with TGF-β1. Collectively, our study identified the role of the UCA1/miR-455/ZEB1 pathway in HUVECs treated with TGF-β1 and indicated the potential therapeutic role of this regulatory axis in angiogenesis.