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Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects synovial membrane 14-3-3η (eta) is a novel protein marker showing potential in predicting radiographic deterioration in early and established RA. The goal of this work was to estimate serum level of 14-3-3 (eta) protein in early and established RA cases and its association with disease activity. Methods: This study was carried out on 50 RA cases and 25 apparently healthy volunteers. The RA cases were classified into group A: 25 cases with early RA (diagnosed within the first three years from the onset of the disease), group B: twenty-five cases with established RA (diagnosed for more than three years of the disease) and group (C) control group: 25 apparently healthy volunteers. All cases were subjected to measurements of. erythrocyte sedimentation rates (ESR) -1st hr -2nd hr, anti-cyclic citrullinated protein antibody (Anti-CCP), and of 14-3-3 eta protein and its association with disease activity. Radiological assessment by sharp/van der hedje scored (SHS), pain was estimated by visual analogue scale (VAS) and disease activity by DAS 28. Results: There is positive association between serum 14-3-3 eta ptn level and all the clinical data (DAS 28, MHAQ, number of tender joints, number of swollen joints and VAS) in both groups (A and B). There is positive association between 14-3-3η ptn and the radiological score in group (A and B). Conclusions: 14-3-3 eta protein is higher in RA cases' serum than that of healthy controls. Adding this test to either RF or both RF and ACPA improved their diagnostic capability for RA. Predicting radiographic deterioration in early and established RA shows promise. Up - regulation of 14-3-3 proteins are linked to adverse consequences. in RA cases.