Abstract Inflammatory external root resorption (IERR) is a pathological process defined by the progressive loss of dental hard tissue, dentin, and cementum, resulting from the combination of the loss of external root protective apparatus and root canal infection. It has been suggested that healing patterns after tooth replantation may be influenced by the genetic and immunological profiles of the patients. The purpose of the present investigation was to evaluate the DNA methylation patterns of 22 immune response-related genes in extracted human teeth presenting with IERR. Methylation assays were performed on samples of root fragments showing IERR and compared with healthy bone tissue collected during the surgical extraction of impacted teeth. The methylation patterns were quantified using EpiTect Methyl II Signature Human Cytokine Production PCR Array. The results revealed significantly higher hypermethylation of the FOXP3 gene promoter in IERR (65.95%) than in the bone group (23.43%) (p < 0.001). The ELANE gene was also highly methylated in the pooled IERR sample, although the difference was not statistically significant (p= 0.054). Our study suggests that the differential methylation patterns of immune response-related genes, such as FOXP3 and ELANE, may be involved in IERR modulation, and this could be related to the presence of root canal infection. However, further studies are needed to corroborate these findings to determine the functional relevance of these alterations and their role in the pathogenesis of IERR.