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Background and Objective: Rheumatoid arthritis (RA) is the most common systemic inflammatory disease. The FOXP3 gene is an agent that activates during the course of the disease and accumulates in the sinus arthritis of the inflamed joints, resulting in persistent inflammation and ultimately tissue damage. Regarding the role of polymorphism in promoter regions in gene expression, this study was conducted to determine the association of rs2232365 polymorphism in promoter of FOXP3 gene with the incidence of rheumatoid arthritis in Iranian population. Methods: In this case-control study, in order to investigate the relationship between FOXP3 gene rs2232365 polymorphism and rheumatoid arthritis, 77 patients and 67 healthy subjects were evaluated. The genotype of individuals for polymorphism rs2232365 was determined by PCR-RFLP method. Results: The highest genotypic frequency was related to CC genotype with 89% frequency in two healthy and diseased populations and no difference was observed in genotypic and allelic abundance in healthy and patient populations. Different genotypes of this polymorphism did not have a significant relation with the risk of RA, while it had a significant correlation with the level of CCP factor and CC genotype was associated with the progression of RA disease by increasing the level of CCP (P