Microglial phagocytic removal of dying cells is critical for tissue homeostasis in the brain. However, recent evidence suggests that excessive phagocytosis could induce death in stressed but still living neuronal cells, which may be closely associated with neuronal diseases. We previously reported that TLR4 activation by LPS promoted removal of dying cells via activating P2Y₂ receptor in rat primary microglia. To clarify the signaling mechanism of P2Y₂ receptor involved in microglial dying cell removal, we investigated a role of proline-rich tyrosine kinase 2 (PYK2), which was shown to mediate phagocytosis in macrophages. LPS stimulation differently modulated gene expression of TAM phagocytic receptors, phosphatidylserine-sensing receptor tyrosine kinases; decrease in MER and increase in AXL. LPS-induced AXL upregulation was inhibited by a selective P2Y₂ receptor antagonist AR-C118925. In addition, LPS stimulation induced an increase in PYK2 expression which was also reduced by AR-C118925. Moreover, a PYK2 inhibitor PF431396 significantly suppressed LPS-induced AXL upregulation. Together, these results suggest that PYK2 may be a key tyrosine kinase downstream of P2Y₂ receptor, facilitating dying cell phagocytosis at least via mediating AXL upregulation in LPS-stimulated microglia.