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Aim: The aim of this study was to evaluate the relationship between Interleukin-6 (IL-6) serum level and the severity and activity of Rheumatoid Arthritis (RA). Methods: In this cross-sectional study, 120 RA patients referred to the rheumatology clinic, the patients were diagnosed by rheumatologists according to ACR / EULAR 2010 criteria. Based on DAS28 score the patients were divided into 4 groups: Remission, Mild, Moderate and Severe. Each group contained 30 patients. Serum levels of Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF) and serum levels of IL-6, were measured. The relationship between these factors was measured and compared to the relationship between IL-6 and these factors, and the activity of the disease was evaluated based on DAS-28. Results: This study showed that the serum level of IL-6 has a significant relationship with RA activity according to DAS-28 (P value <0.001). There is also a significant relationship between the ESR level, the number of painful joints, and the number of swollen joints, and the severity of the disease based on VAS. Conclusion: Generally the findings of this study indicate that serum level of IL-6 plays an important role in the severity and activity of RA disease and can be considered as a determining factor in evaluating the severity of RA in RA patients and it is a good guide for a step up or down of treatment.