Reproductive ageing in females is defined by a progressive decline in oocyte number and quality. This is a natural process that leads to the loss of fertility and ovarian function, cycle irregularity and eventually menopause. The factors that underlie the natural depletion of oocytes throughout reproductive life are poorly characterised. In this study, we investigated the hypothesis that inflammation contributes to the loss of oocytes as females age. We first determined oocyte numbers and characterised the systemic and local ovarian inflammatory phenotype in C57/Bl6 mice at 2, 6, 12 and 18-months of age. This period of time spans the onset of sexual maturity to the end of female fertility in mice. We observed that the decrease in oocyte numbers over the reproductive lifespan was associated with an increase in the serum concentration and intra-ovarian mRNA and protein levels of pro-inflammatory cytokines IL-1α/β, TNF-α, IL-6, and inflammasome proteins ASC and NLRP3. To gain further insight into the possible role of the NLRP3 inflammasome in oocyte depletion, we compared oocyte numbers in wild type (WT), nlrp3-/- and asc-/- mice (n=3-6/genotype). We found that while oocyte numbers were similar in WT and nlrp3-/- mice at 12 months of age, the primordial follicle reserves remained extremely high in asc-/- mice (WT= 253±76 vs asc-/-= 824±96, p=0.0051). Notably, levels of some pro-inflammatory cytokines in the serum of asc-/- mice were found to be significantly lower compared to WT (for IL-6: WT= 4.5±0.9 vs asc-/-= 2.0±0.5, p=0.0341). These data strongly implicate inflammation as a causative factor in the age-associated depletion of oocytes and raises the possibility that ovarian ageing could be delayed, and fertility prolonged, by suppressing inflammatory processes in the ovary.