Background: Rheumatoid Arthritis (RA) is a chronic progressive, systemic inflammatory, connective tissue disease affecting approximately 1% of the general population. Interleukin-33 (IL33), a member of the IL-1 family, is a ligand for the orphan receptor ST2 (known as IL-1RL1 also). IL-33 is crucial for Th2 cytokine-mediated immune responses however; it can overcome this role in RA. Aim: This study aimed to investigate the potential role of inflammatory cytokine (IL-33) in RA and assess the correlation of IL-33 level to disease activity. Subjects and Method: The study included sixty patients with RA. Patients were diagnosed according to the American College of Rheumatology (ACR) 2010 revised criteria and were classified into 2 groups of 30 patients each according to disease activity score 28 (DAS28), the first group included RA patients with DAS28 of ≤2.4 and the second group included RA patients with DAS28 >2.4.Thirty normal subjects served as a control group. Serum IL-33 was measured using ELISA. Results: Serum IL33 level was significantly higher in patient's group compared to the control group (P ≤.001). Also, serum IL33 level, was significantly higher in patients' group 2 (DAS>2.4) than patients' group 1 (DAS≤2.4) (P<0.001). Serum IL-33 level positively correlated with disease duration, ESR, CRP and disease severity. Conclusion: IL-33 is a novel potential marker for the risk of RA as well as a marker of disease activity