tPhagocytosis, an evolutionarily conserved process in animals, plays a central role in host defense againstpathogens. As reported, Rab6 GTPase was involved in the regulation of hemocytic phagocytosis ininvertebrates. However, the role of Rab6 GTPase in mammalian phagocytosis remains to be addressed.In this study, the results showed that Rab6 GTPase took great effects on phagocytosis of mouse leukemicmonocyte macrophages (RAW 264.7 cells). It was revealed that Rab6 GTPase was required during thephagosome maturation by its interaction with bicaudal-D1 (BICD1) protein. Further data presented thatthe Rab6 GTPase-regulated phagocytosis could influence the proliferation of Staphylococcus aureus inmacrophages. Therefore, our study demonstrated a novel insight into the mechanism of regulation ofmammalian phagocytosis by Rab6 GTPase and a novel strategy for the control of Staphylococcus aureus.