Brain aging often results in cognitive impairment and is considered to be a major risk factor for neurodegenerative diseases. Earlier studies reported inflammatory responses in aged brain that could contribute to age-related neurodegeneration. Recently, innate immune receptors such as toll-like receptors (TLRs), so far implicated in defense against microorganisms, have been linked to pathogenesis of Alzheimer’s disease. Therefore, we asked whether the transcription of TLRs (1–9) and CD14, could also be altered in physiological brain aging. Using real-time polymerase chain reaction (PCR), we indeed observed that TLR1, TLR2, TLR4, TLR5, TLR7 and CD14 expression was up-regulated in mouse brain in correlation with age. In contrast, transcriptions of TLR3, TLR6 and TLR8 were unchanged and the one of TLR9 was down-regulated. In situ hybridization further confirmed these results and identified the cellular source of TLR2 and TLR7 as mononuclear phagocytes. Together, this first systematic analysis demonstrates altered regulation of those innate immune receptors even in normal brain aging, which might be of relevance for understanding susceptibility to neurodegenerative processes associated with aging.