Background: Pain, swelling, soreness from touching, stiffness in the joints, particularly in the morning, and symmetrical polyarthritis are all symptoms of rheumatoid arthritis (RA), a prevalent form of autoimmune inflammatory arthritis. Objective: This work was aimed to investigate whether there is a correlation between the expression of the nuclear factor kappa beta1/IKK epsilon (NF-κB1/IKKε) gene and disease activity indices in individuals who have early rheumatoid arthritis. Patients and Methods: This study involved 50 patients with newly diagnosed RA and 30 subjects serving as controls. Patients were subjected to detailed medical history, clinical examination, and underwent evaluation of illness severity using disease severity scores (DAS-28). Laboratory investigations, and real time PCR was done for NF-B1/IKK. Examination using power Doppler ultrasonography (PDUS) was carried out on 22 of the joints that were affected by RA. Results: NF-κB1 and IKKε gene expression levels were significantly increased in cases with positive RF and Anti-CCP compared to patients without (p < 0.001 for both). Also, according to disease activity; the higher the activity the more NF-κB1 and IKKε gene expression levels with significant differences (p <0.001). Higher erythrocyte sedimentation rate (ESR), PDUS, NF-κB1 and IKKε gene expression levels were associated with risk of higher DAS grades in univariable analysis (p=0.007, 0.023, 0.011, 0.002 respectively). However, in multivariable analysis, only higher NF-κB1 and IKKε gene expression levels were considered independent predictors of higher DAS grades (p=0.019, 0.044 respectively). Conclusion: Our findings suggest that NF-κB1 and IKKε play an important role in RA pathogenesis and could be considered as an activity indicator.