Thromboxane synthase (TXAS) and thromboxane A₂ receptor (TP), two critical components for thromboxane A₂ (TXA₂) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA₂ promotes these processes are still unclear. Here we show that TXA₂ mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor α isoform (A549-TPα). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPα cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA₂ may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment.