Aim: The aim of this study was to evaluate the relationship between Interlukin-6 (IL-6) serum level and the severity and activity of 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 Based on DAS28 score the patients were divided into 4 groups: Remission, Mild, Moderate and Severe. Each group contained 30 patients. Serum levels of ESR, CRP, anti-cyclic citrullinated peptide (anti-CCP) and RF, as well as serum levels of IL-6, were measured in these patients. Then, the relationship between these factors in the four groups was measured and compared, and the relationship between IL-6 and these factors, and especially the severity 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 severity 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 the swollen joints, and the severity of the disease based on VAS. Conclusion: generally the findings of this study indicate that serum levels 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 severity of RA in RA patients and it is a good guide for step up or down of treatment.