The aim of the present study was to determine Toll-like receptor (TLR)-2 and TLR-4 membrane expression on the major peritoneal leukocyte populations throughout the aging process, including subjects that had achieved exceptional longevity. ICR (CD1) female mice of different ages: adult (44 +/- 4 weeks), old (69 +/- 4), very old (92 +/- 4) and extreme long-lived (125 +/- 4), were used. Peritoneal leukocytes were collected, and percentages of CD11b, CD11c, CD3CD4, CD3CD8 and CD19 cells present in the samples were analysed, as well as the expression of TLR-2 and TLR-4 on them, by flow cytometry. The results showed increased TLR expression on CD11b+ cells from animals at very old ages and especially in the extreme long-lived. Old subjects showed lower percentage of CD11c+ cells, but no age-related changes were found in the TLR expression on these cells. TLRs on CD3CD4+ and CD3CD8+ cells from very old animals were increased as compared to the adults, whereas long-lived subjects showed preserved levels. However, TLR expression on CD19+ cells was higher in long-lived individuals with respect to subjects at all the other younger ages. These data suggest that differential age-related changes in the expression of TLR-2 and TLR-4 on leukocyte populations from long-lived and non-selected younger old mice could contribute to a different age-related immune remodelling in long-lived subjects, which could allow better preservation of their immune responses.