Annexin-1 (ANX1) is an anti-inflammatory protein as well as an important modulator in inflammation. However, the precise action of ANX1 remains unclear. To elucidate the protective effects of ANX1 on lipopolysaccharide (LPS)-induced murine macrophage Raw 264.7 cells, we constructed a cell-permeable Tat-ANX1 protein. The transduced Tat-ANX1 protein markedly inhibited the expression of cyclooxygenase-2, production of prostaglandin $E_2$, and generation of pro-inflammatory cytokines in the cells. Furthermore, transduced Tat-ANX1 protein caused a significant reduction in the activation of nuclear factor-kappa B (NF-${kappa}B$) and mitogen-activated protein kinase (MAPK). The results indicate that Tat-ANX1 inhibits the production of inflammatory response cytokines and enzymes by blocking NF-${kappa}B$ and MAPK. Therefore, Tat-ANX1 protein may be useful as a therapeutic agent against various inflammatory diseases.