Ageing is the most significant contributory factor in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, and inflammatory changes in the brain contribute to the deficits associated with aging and neurodegenerative disorders. Fundamental to these changes is an increase in microglial activation, the immune cells of the brain, which are the primary source of pro-inflammatory cytokines. Microglial activation has been shown to be induced by IFN-γ (1), a macrophage-activating factor, but the cell source of IFN-γ in the central nervous system is not known. IFN-γ is produced by Natural Killer (NK) cells, which are traditionally found in the peripheral nervous system, and the finding that IFN-γ concentration is increased in the brain of aged rats suggests a possible infiltration of NK cells into the CNS. In this study young (2-3 month old), middle-aged (14-15 month old) and aged (18-25 month old) male Wistar rats (n=6 per group) were anaesthetised (i.p.) with urethane, and intracardially perfused with saline. Dissociated cells were prepared from one half of the brain and assessed, using flow cytometry, for the presence of NK cells. Cortical and hippocampal tissue taken from the other half of the brain was assessed for IFN-γ mRNA, and expression of markers of microglial activation, MHCII, CD11b, TLR2 and TLR4. The data demonstrate that NK cells are present in the rat brain and that the number of cells positive for NK cell markers, CD161a and NKp30, was significantly greater in brain tissue prepared from aged, compared with middle aged, rats (p<0.05; Student’s t-test). This finding was associated with a significant age-related increase in cortical and hippocampal mRNA expression of MHC II (p<0.05; 1-way ANOVA) and CD11b (p<0.001; Student’s t-test). These results were also coupled with age-related increases in hippocampal IFN-γ, TLR2 and TLR4 mRNA (p<0.05; Student’s t-test). These findings provide the first evidence for the presence of NK cells in the aged rat brain, and suggest a possible role for NK cells in the activation of microglia during age-related neuroinflammation.