Background: Rheumatoid arthritis [RA] is one of the most common chronic, inflammatory autoimmune disease with a frequency of 0.5–1.0% between the adult population of developed countries. It is marked by chronic inflammation of synovial tissue and accompianed by damage of the articular cartilage and adjecent bone, leading to substantial disability. Objectives: The aim of this study is to determine serum and synovial fluid levels of calprotectin in rheumatoid arthritis patients and to determine its relation with disease activity and severity. Methodology: This study was carried out on 40 rheumatoid arthritis patients who were admitted to Rheumatology, Rehabilitation and Physical Medicine Outpatient' clinic and Inpatient Department of Benha University Hospital .Also Thirty age and sex matched( 28 females and 2 males ) apparently healthy volunteers were included in the study as a control group . All patients were assessed by full medical history, clinical examination, functional assessment, laboratory investigations including CBC, ESR ,CRP, liver functions, RF, Anticcp antibody, and X-rays were done to both hands. Serum and synovial levels of calprotectien were measured using the ELISA technique. Results: Serum levels of calprotectien were significantly higher in RA patients than healthy subjects [p<0.001], also there was a highly statistically significant increase in the mean synovial fluid calprotectin levels than mean serum calprotectien levels [p<0.001]. Local and systemic levels of calprotectin correlate with clinical, immunological and instrumental assessments of disease activity and the inflammatory degree of the joint. Conclusion: Calprotectin could be used as a new biomarker for monitoring the disease activity and severity of RA. Larger sets are needed to confirm the diagnostic and prognostic accuracy of calprotectin in RA.