Astrocytes respond to neuronal activity by propagating Ca²⁺ waves elicited through the inositol 1,4,5‐trisphosphate pathway. We have previously shown that wave propagation is supported by specialized Ca²⁺ release sites, where a number of proteins, including inositol 1,4,5‐trisphosphate receptors (IP₃R), occur together in patches. The specific IP₃R isoform expressed by astrocytes in situ in rat brain is unknown. In the present report, we use isoform‐specific antibodies to localize immunohistochemically the IP₃R subtype expressed in astrocytes in rat brain sections. Astrocytes were identified using antibodies against the astrocyte‐specific markers, S‐100β, or GFAP. Dual indirect immunohistochemistry showed that astrocytes in all regions of adult rat brain express only IP₃R2. High‐resolution analysis showed that hippocampal astrocytes are endowed with a highly branched network of processes that bear fine hair‐like extensions containing punctate patches of IP₃R2 staining in intimate contact with synapses. Such an organization is reminiscent of signaling microdomains found in cultured glial cells. Similarly, Bergmann glial cell processes in the cerebellum also contained fine hair‐like processes containing IP₃R2 staining. The IP₃R2‐containing fine terminal branches of astrocyte processes in both brain regions were found juxtaposed to presynaptic terminals containing synaptophysin as well as PSD 95‐containing postsynaptic densities. Corpus callosum astrocytes had an elongated morphology with IP₃R2 studded processes extending along fiber tracts. Our data suggest that PLC‐mediated Ca²⁺ signaling in astrocytes in rat brain occurs predominantly through IP₃R2 ion channels. Furthermore, the anatomical arrangement of the terminal astrocytic branches containing IP₃R2 ensheathing synapses is ideal for supporting glial monitoring of neuronal activity. GLIA 39:69–84, 2002. Published 2002 Wiley‐Liss, Inc.