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Both rheumatoid arthritis and periodontitis are complex multifactorial disorders, characterized not only by a dysfunction of basic inflammatory and tissue destructive mechanisms, but also by an altered adaptive and innate immune response in individuals. IL-22 plays an important role in inflammation, including chronic inflammatory diseases and infectious diseases. This study aimed to evaluate the serum levels of IL-22 and ACPA in RA patients. The study included 45 rheumatoid arthritis patients and 35 apparently healthy controls. Enzyme-linked immunosorbent assay (ELISA) has been used for estimation the levels of IL-22 and ACPA in serum of two studied groups. The present results revealed that mean serum levels of IL-22 and ACPA were significantly higher in patients than in healthy controls (p<0.02, p<0.04) respectively. On the other hand, there is no correlation was found between serum level of antibody (IgG-ACPA) and serum level of cytokine (IL-22), (r=0.79; p=0.606). Elevation serum level IL-22 could be involved pathogenesis of RA in association with ACPA level.