AbstractThe expression of CB2 cannabinoid receptors (CB2‐Rs) in the brain and their neuronal function has now attracted research interest, since we and others have demonstrated the presence of CB2‐Rs in neuronal and glial cells in the brain. In this study, we show the subcellular distribution of CB2‐Rs in neuronal, glial, and endothelial cells in the rat hippocampus using immunohistochemical electron microscopy. Brain sections from the hippocampus were immunolabeled for CB2‐R, visualized, and analyzed by electron microscopy. We found that in neurons, CB2‐R immunoreactivity is present in the cell body as well as in large and medium‐sized dendrites. In the soma, the CB2‐R labeling is associated with the rough endoplasmic reticulum and Golgi apparatus demonstrating that CB2‐Rs are synthesized by hippocampal neurons. CB2‐R labeling in dendrites was observed in the cytoplasm and associated with the plasma membrane near the area of synaptic contact with axon terminals indicating a postsynaptic distribution of these receptors. In CB2‐R immunoreactive glial and endothelial cells, the labeling was also found to be associated with the plasma membrane. These results provide the first ultrastructural evidence that CB2‐Rs are mainly postsynaptic in the rat hippocampus. Synapse 62:944–949, 2008. © 2008 Wiley‐Liss, Inc.