Epithelial-mesenchymal interactions have been found to play a role in the pathogenesis of odontogenic keratocyst (OKC). In the present study we investigated the effect of inflammation in the OKC wall on the polarization colors of Picrosirius red-stained collagen fibers. 50 cases of OKC were selected and separated into two groups according to the inflammatory intensity: those with mild-to-moderate inflammation (Group A), and those with intense inflammation (Group B). The polarization colors of the collagen fibers were recorded separately for thick and thin fibers. Polarization colors of the thin fibers were in the green- to yellow spectrum, without significant differences between the groups. However, polarization colors of the thick fibers significantly differ between the groups. In Group B, the frequency of thick fibers with green birefringence decreased significantly, whereas fibers with red polarization colors increased in frequency (4.6% and 44%, respectively) compared with Group A (12.3% and 23.6%, respectively). It can than be concluded that inflammation has an impact on the packing of collagen fibers in the connective tissue wall of OKC as reflected by their birefringence colors under polarized light. In the presence of dense inflammation, the percentage of thick fibers with green birefringence decreases, with an increase in thick fibers with red birefringence which appeared more packed.