Abnormal migration of retinal pigment epithelium (RPE) contributes to a variety of disorders such as proliferative vitreoretinopathy. Here, the effect of epidermal growth factor (EGF), and signaling by its receptor (ERGR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) on RPE cell migration was studied. The in vitro wound healing and migration of the human RPE cell line, ARPE19 cell was accelerated, in a dose dependent manner, in response to EGF stimulation, while pretreatment with EGFR, PI3K or AKT inhibitor, inhibited both events. Exposure of cells to EGF activated the AKT phosphorylation, whereas EGFR and PI3K inhibitors blocked EGF-induced AKT phosphorylation in a dose-dependent manner. These data suggest that EGF mediate ARPE-19 cell migration through EGFR/PI3K/AKT signaling pathway.