Background: In the periphery, C5a acts through the G-protein coupled receptor CD88 to enhance/maintain inflammatory responses. In the brain, CD88 can be expressed on astrocytes, microglia and neurons. Previous studies have shown that the hippocampal CA3 region displays CD88-immunolabelling, and CD88 mRNA is present within dentate gyrus granule cells. As granule cells send dense axonal projections (mossy fibres) to CA3 pyramidal neurons, CD88 expression could be expressed on mossy fibres. However, the cellular location of CD88 within the hippocampal CA3 region is unknown. Methods: The expression of CD88 within the hippocampal CA3 region was characterized using dual-immunolabelling of hippocampal sections prepared from Wistar rats. Immunolabelling for CD88, using a monoclonal antibody, was combined with immunolabelling for markers of astrocytes (GFAP), microglia (IBA1), presynaptic proteins (synaptophysin and synapsin-1) and preterminal axons (neurofilament). In addition, electron microscopy was performed on peroxidase-visualized CD88-immunolabelling to determine its cellular localisation within the CA3 region. Results: Dense CD88-immunolabelling was observed within the stratum lucidum of the CA3, consistent with the presence of CD88 on mossy fibres. Labelling for CD88 rarely co-localized with astrocytes or microglia, but was highly co-localized with presynaptic proteins. Electron microscopy revealed CD88-immunolabelling was localized to large presynaptic terminals within the stratum lucidum. Conclusion: These results demonstrate that CD88 is expressed on presynaptic terminals of mossy fibres within the CA3 region of the hippocampus. Although the role of CD88 on mossy fibres remains to be established, their involvement in synaptic/cellular plasticity, and in cognitive disorders such as Alzheimer's disease deserves investigation.