Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human and mouse MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of both humans and mice. However, Tie2 was not detected on the cell surface of the mouse MCs of the peritoneal cavity, ear skin, or colon lamina propria. In contrast, it was expressed on mouse bone marrow-derived MCs and bone marrow MC progenitors (BM-MCps). Stimulation of Tie2 by its ligand angiopoietin-1 induced tyrosine phosphorylation of Tie2 in MEDMC-BRC6, a mouse embryonic stem cell-derived mast cell line, and enhanced MEDMC-BRC6 and mouse BM-MCp adhesion to vascular cell adhesion molecule-1 (VCAM-1) through α4β1 integrin. These results suggest that Tie2 signaling induces α4β1 integrin activation on BM-MCps for adhesion to VCAM-1.