Either phagocytosis of macrophage to pathogen or pathogen-induced invasion into non-professional phagocytes, such as epithelial cells, require actin cytoskeletal rearrangements and remodeling of the plasma membrane, which are regulated precisely by monogeric GTPase and the correlated proteins. As a key signaling molecule in the cell, phosphotidicphospholipase D (PLD) regulates or interacts directly with cellular actin cytoskeleton rearrangement. Phospholipase D plays an important role in FcgammaRI and C-reactive protein-mediated phagocytosis and phosphorylated cofilin, a ADF (actin depolymerizing factor) is able to bind to phospholipase D and stimulate it; meanwhile, the Listeria-induced actin cytoskeleton rearrangement during the infection is controlled by the phosphorylation of cofilin. Thus, it made challenge to disclose the function of PLD on the regulation of Listeria-induced actin cytoskeleton rearrangement during infection, furthermore, it may provide us more understanding on the role of PLD in the infection and inflammation, which is essential to dissect the molecular mechanism of bacterial-host interaction more thoroughly.