Rheumatoid arthritis is a systemic autoimmune disease with different factors contributing to the etiology and pathogenesis. The aim of this study is to assess the role of Mycoplasma infection, to determine the association of IL-1 gene polymorphism and to assess the role of CD4+CD25+ Regulatory T cells in RA. The study was conducted on 50 adult RA patients and 10 controls. Results indicated that IL-1β (+3953) gene polymorphism is related to RA activity, but plays no role in RA susceptibility; IL-1Ra gene polymorphism (IL1RN*2) plays no role in RA susceptibility or activity; a positive significant correlation exists between the numbers of CD4+CD25+ T cell and disease activity and that association of Mycoplasma fermentans to RA susceptibility and/or severity could not be clearly elucidated. In conclusion, It was shown that the presence of allele 2 of IL-1β gene and the increase in circulating CD4+CD25+ cells number in RA might be cosidered as prognostic factors for RA more than the effect of IL-1Ra gene polymorphism or the infection with M. fermentans.