Prostaglandin endoperoxide H synthases and their arachidonate products have been implicated in modulating angiogenesis during tumor growth and chronic inflammation. Here we report the involvement of thromboxane A₂, a downstream metabolite of prostaglandin H synthase, in angiogenesis. A TXA₂ mimetic, U46619, stimulated endothelial cell migration. Angiogenic basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) increased TXA₂ synthesis in endothelial cells three- to fivefold. Inhibition of TXA₂ synthesis with furegrelate or CI reduced HUVEC migration stimulated by VEGF or bFGF. A TXA₂ receptor antagonist, SQ29,548, inhibited VEGF- or bFGF-stimulated endothelial cell migration. In vivo, CI inhibited bFGF-induced angiogenesis. Finally, development of lung metastasis in C57Bl/6J mice intravenously injected with Lewis lung carcinoma or B16a cells was significantly inhibited by thromboxane synthase inhibitors, CI or furegrelate sodium. Our data demonstrate the involvement of TXA₂ in angiogenesis and development of tumor metastasis.