Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune synovitis. The etiopathogenesis of RA remains unidentified. Nonetheless, autoimmune mechanisms have a role in its pathomechanism. It was reported that the chronic inflammatory process in RA is associated with synovial proliferation, which is linked to cartilage and bone resorption. YKL-40 is a primary protein produced from arthritic joints by chondrocytes in vitro and in vivo. It has been demonstrated that its value is markedly increased in the context of joint disorders such as RA and osteoarthritis (OA). Objective: This study aimed to evaluate serum YKL-40 concentrations in RA patients compared to healthy individuals and to investigate the association between serum YKL-40 levels with disease activity in RA. Patients and Methods: This study included 35 RA patients with mean age of 42.23 ± 9.94 years, 6 (17.1%) males & 29 (82.9%) females. 35apparently healthy individuals with mean age of 39.46 ± 8.28 years, 10 (28.6%) males & 25 (71.4%) females. Laboratory investigations were done. Serum YKL-40 was analyzed and DAS28 was evaluated. Results: RA cases were linked to a significant increase in YKL-40 levels compared to controls. Serum YKL-40 level was significantly correlated with RA activity (P=0.001) (DAS28). There were statistically significant increases in Anti-CCP, rheumatoid factor (RF), CRP, ESR, WBCs and platelet in RA cases than in the controls. Conclusion: Serum YKL-40 was significantly increased with RA as well as with its activity. It could be used as a valid marker in the context of RA diagnosis.