Fibroblast growth factors (FGFs) are polypeptides that exert diverse biological effects on many cell types and tissues during embryogenesis and adulthood. In the adult brain, FGF-2 is primarily expressed by astrocytes and select groups of neurons. It has been shown that FGF-2 is neuroprotective and can stimulate proliferation of NSCs in neurogenic regions of the adult mammalian brain. Cellular responses to FGFs are mediated through membrane-spanning tyrosine kinase receptors in conjunction with low affinity binding to heparin sulfate proteoglycans. Four FGF receptors (FGFR1–4) have been cloned and characterized to date. In this study, we describe the anatomical distribution of FGFR-2 in young and aged rat brains. We demonstrate that the olfactory bulb, hippocampus, and cerebellum display the most robust FGFR-2 expression and observed age-related decrease in FGFR-2 levels in some but not all brain regions. In addition, we identified astrocytes as the primary source of FGFR-2 expression using immunofluorescence confocal microscopy. The astrocyte populations in the neurogenic areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus, express high levels of FGFR-2 protein, which points to its possible involvement in neurogenesis. We also explored the role of FGFR-2 in response to perforant pathway lesion and observed enhanced FGFR-2 expression by astrocytes surrounding the lesion. Thus, FGF-2 biological effects on astrocytes appear to be mediated through FGFR-2-dependent mechanisms, and this may provide an indirect route by which FGF-2 acts on neuronal populations. J. Comp. Neurol. 498:1–15, 2006. © 2006 Wiley-Liss, Inc.