Moesin is a member of the ezrin, radixin and moesin proteins that are involved in the formation and/or maintenance of cortical actin organization through their cross-linking activity between actin filaments and proteins located on the plasma membranes as well as through regulation of small GTPase activities. Microglia are immune cells in the central nervous system. They show dynamic reorganization of the actin cytoskeleton in their process elongation and retraction as well as phagocytosis and migration. They also secrete proinflammatory cytokines such as tumor necrosis factor−α (TNF−α). Moesin is the predominant ezrin, radixin and moesin family protein in microglia. Recently, we found that moesin is involved in microglial activation accompanying morphological changes and reorganization of actin cytoskeleton by using moesin knockout mice in vivo and ex vivo. Here we studied the effects of a small molecule inhibitor specific for ezrin and moesin, NSC305787, on the moesin phosphorylation, phagocytosis, migration, and TNF−α secretion of the primary microglia. NSC305787 at the concentration of 10 μM inhibited the moesin phosphorylation, UDP-induced phagocytosis, ADP-induced migration and lipopolysaccharide-induced TNF−α secretion without effect on cell viability. These results in combination with the previous results using moesin knockout mice suggest the functional importance of moesin in microglial activities.