Nerve injury in trigeminal ganglion (TG) neurons occasionally induces neuropathic pain in maxillofacial region. As a part of developmental mechanisms in neuropathic pain, ATP receptors play key roles in pain signaling. These ATP receptors are exists on cell membrane and classified into ionotropic P2X (subdivided into P2X1-7) and G-protein-coupled P2Y (subdivided into P2Y1, 2, 4, 6, 11-14) receptors. Sufficient evidence shows expression of P2X3, and P2X2/3 on sensory neurons, and that of P2X4, P2X7 and P2Y12 on glial cells. Activation of Gαi following P2Y12 receptors activation inhibits adenylate cyclase in cells at brain (in particular glial cells), spinal cord and platelets. The P2Y12 receptors interact with some molecules (e.g. P2X4 receptors, chemokine receptors, toll-like receptors, mitogenactivatedprotein kinase, Src-family kinase and cathepsin S) in activated micro or satellite glial cells and induces neuropathic pain. P2Y12 receptors are also expressed in satellite glial cells in injured TG neurons, and its activation enhances neuronal activity. Thus, expression and neuro-pathological role of P2Y12 receptors has been well described in the glial cells, however, their expression and physiological roles of P2Y12 receptor in the TG neurons remain to be clarified. In the present study, we investigated expression, localization, physiological and pharmacological properties of P2Y12 receptors by mmunofluorescence analysis, and measurement of intracellular free Ca2+ concentration ([Ca2+]i) with fura-2 fluorescence in the primary cultured rat TG neurons. We observed intense immunoreactions for P2Y12 receptors on soma, dendrites and axons in TG neurons, which co-localized with Pan-neuronal marker, neurofilament 200, isolectin B4, and substance P. In the presence or absence of extracellular Ca2+, application of P2Y1,12,13 agonist (2-MeS-ADP) increased [Ca2+]i transiently with dose-dependent manner. These increase in [Ca2+]i was not observed in the presence of sarcoplasmic reticulum Ca2+-ATPase inhibitor (cyclopiazonic acid) with or without extracellular Ca2+. Moreover, these 2-MeS-ADP-induced increase in [Ca2+]i were significantly inhibited by selective P2Y12 receptor antagonists (AR-C66096 and PSB0739) in the presence of extracellular Ca2+ . These results showed that P2Y12 receptor distribute A-, non-peptidergic C- and peptidergic C-neurons; and indicate that activation of P2Y12 receptors induced release of Ca2+ from the intracellular Ca2+ stores. Further study is needed how an activation of P2Y12 receptors in TG neurons contribute to pain signaling in oral and maxillofacial region.