In this context, the purpose of this study was to investigate the potential mechanisms involved in the spontaneous onset of diabetes-triggered periodontitis through the quantitative and spatial evaluation of RAGE, TNF-alpha, IL-1beta, IL-6, RANKL, MMP-2, MMP-9 immunostaining patterns, and also the monitoring of oral microbiota load, in periodontal tissue in rats after 1, 3, 6, 9, and 12 months of diabetes induction. This evidence concerns the gene TNFSF11 and diabetes mellitus.