OBJECTIVE 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. CONCLUSIONS 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.