Recurrent Aphthous Ulceration (RAU) is a chronic oral inflammatory disease that affects approximately 25% of the general population. The etiology of the disease is unknown; however, factors that favor the onset of RAU have been correlated with a Th1 immune polarization, while factors that reduce RAU episodes have been associated with down regulation of immune reaction or stimulation of the peripheral tolerance. In this context, the integrity of the epithelial barrier is also fundamental for the prevention of the disease and conditions that augment its permeability or produce disruption are considered potential triggers. The key factor responsible for increased susceptibility is unclear, though a deficiency of Toll-like receptor (TLR) activity seems to be a good candidate. TLRs are a group of membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal, or host tissues. Particularly, the TLR2 is involved in both immune regulation and control of epithelial barrier integrity. Thus, based on literature review, we showed evidences that correlate the TLR2 dysfunction and the diverse predisposing factors with the elements considered critical for disease pathogenesis: the Th1 immune reaction and the increased epithelial permeability.