Pemphigus foliaceus (PF) is an autoimmune skin disease in which environmental factors are thought to participate. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in keratinocytes. The aim of our research was to investigate the expression of TLRs 2, 3 and 4 by keratinocytes of PF patients compared to normal keratinocytes, in order to characterise the nature of the microbial factor involved in the etiopathology of PF. Biopsies obtained from 43 PF patients and 20 healthy controls were assessed by immunohistochemical analysis using specific polyclonal antibodies. The TLR2, TLR3 and TLR4 expression was significantly upregulated in PF epidermis. The significant increase of those TLRs simultaneously may merely reflect the complicated environmental conditions of rural women in the southern rural regions of Tunisia. Interestingly, we have found that the TLR4 diffuse expression was associated with the production of anti-desmoglein 1 Abs (p=0.037). This could be in line with a potential role of TLR ligand in aethiopathogenesis of Tunisian endemic PF.TLR over-expression in pemphigus skin indicates that TLRs are involved in the pathogenesis of pemphigus through stimulation by infectious or endogenous ligands.