Objective To investigate the distribution of histone deacetylase 2 (HDAC2) in the hippocampus of adult C57BL/6 mice and the co-localizations of HDAC2 and PSD components, such as N-methyl-D-aspartate (NMDA) receptor 1 (NR1) and PSD-95, and provide morphological evidence for inherent relationship between postsynaptic density (PSD) components in synapses and HDAC2 in nucleus. MethodsThe morphology and distribution of HDAC2 positive neurons in the hippocampus were observed by immunohistochemistry. The hippocampal distributions of NR1 and PSD-95, as well as co-location with HDAC2 were detected using double immunofluorescence staining. ResultsHDAC2 immunoreactivity was mainly observed in hippocampal CA1-CA3 pyramidal cells and dentate gyrus granule cells. The scattered positive cells were accidentally present in the oriens layer, radiate layer and lacunosum-moleculare layer of CA1-CA3 and molecular layer and polymorphic layer of dentate gyrus. The distributions of NR1 and PSD-95 positive neurons are similar to that of HDAC2 positive neurons in the hippocampus. The co-location analysis showed that almost all HDAC2 immunoreactive neurons observed in pyramidal cells of CA1-CA3 and granule cells of dentate gyrus. Conclusions HDAC2 is rich in hippocampal pyramidal cell layer and granule cell layer, and co-located with PSD proteins. The results provide a morphological clue to explain the role of HDAC2 in postsynaptic glutamatergic neuron-dependent synaptic plasticity. 