Adiponectin considered the most abundant adipokine in the body, is a prime example. The development of RA causes the irreversible joint deformity, disability, and a decrease in quality of life. The study aimed to investigate the role of Adiponectin in rheumatoid arthritis patients under biological treatment (ETN, and RTX) and their correlation with Disease activity. During December 2021 and May 2022, case-control research was conducted. The current study included 100 RA patients from Iraq who had registered consultations with rheumatologists. The American-European Consensus Group classification criteria for RA diagnosis and patients were chosen to receive ETN and RTX by the most recent recommendations, and 50 healthy control group. ELISA was used to assess anti-CCP abs and serum adiponectin in RA patients and control groups. In the comparison, the level of Adiponectin in the serum of RA patients under DMARDs was significantly higher (p<0.001) than in the control group. The correlation between auto-antibody (anti-ccp) and adiponectin was a highly significant (r = 〖.533〗^(**)). There is a highly significant correlation between moderate and high CDAI, p-value <0.001. In addition to There are an association of adiponectin with biological treatment (OR = 1.003, p-value = .001, 95% CI = 1.002- 1.005). The sensitivity and specificity of adiponectin were (1.0, 0.80) respectively by ROC curve with cut of point (400,603) pg/gm. The current study concluded high levels of circulating Adiponectin in RA patients have been linked to increased disease activity and disability. Despite continuing to receive Etanercept and Rituximab treatment, there was a positive correlation between the serum levels of adiponectin and the specific diagnostic autoantibody Anti-CCP abs level in patients with rheumatoid arthritis. As a result, it has been hypothesized that this adipokine may have pro-inflammatory effects in rheumatoid arthritis.