Lymphangiogenesis has functional consequences not only for lymphatic transport, but also for inflammation resolution. Thromboxane A2 (TxA2) has been suggested to involve not only in induction of inflammation, but also in resolution of inflammation. We investigated the functional role of TxA2 receptor (TP) signaling in inflammation-associated formation of newly lymphatic vessels. Lymphangiogenesis in the diaphragm of TP knockout mice (TPKO) or their wild-type (WT) counterparts was induced by repeated intraperitoneal injection of LPS. Compared with WT, LPS-induced lymphangiogenesis in TPKO was suppressed, which was accompanied by reduced expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in CD11b+ and CD4+ cells in diaphragm tissue. TP was expressed in CD11b+ and CD4+ cells, but not in LYVE-1+ cells (lymphatic vessels). U46619, an agonist for TxA2, did not proliferate cultured lymphatic endothelial cells. As compared with controls, mice with macrophage TP receptor deletion showed attenuation of lymphangiogenesis with reduced expression of VEGF-C and VEGF-D. When fluorescein isothiocyanate (FITC)-dextran was injected into the peritoneal cavity, the amount of residual FITC-dextran in macrophage-specific deletion of TP receptor was greater than that in controls. The same was true for mice with T cell TP receptor deletion. The present results suggest that TP signaling in macrophages and T cells plays a critical role in inflammation-related lymphangiogenesis and drainage function of lymphatics in the diaphragm.