Abstract Background: CX3C Chemokine Receptor 1 (CX3CR1) is a chemokine receptor which interact with the pro-inflammatory chemokine fractalkine and participates in the pathology of inflammatory arthritis. Aim of Study: This study aimed to evaluate the variations of CX3CR1 in rheumatoid arthritis. Subjects and Methods: A case-control study involved 50 male and female Rheumatoid Arthritis (RA) cases and 25 healthy controls. Disease activity, Anti-Cyclic Citrullinated Peptide (Anti-CCP), Erythrocyte Sedimentation Rates (ESR), Rheumatoid Factor (RF), C-Reactive Protein (CRP) were evaluated as well as assessment of the variations in CX3CR1 by Flowcytometric studies or Polymerases Chain Reactions (PCR). Results: A significant link was detected between RA and CX3CR1 (p=0.0001) with three types of genotyping detected using high resolution melting PCR as; AA constituted the highest percentage in cases (28%) compared to controls (20%), AG was detected in 21 cases (42%) and not detected in controls (0%) and GG was detected in 15 cases (30%) versus 20 controls (80%). Also, cases showed significant increase in median flow than the control (4.8 vs. 1.26 respectively) (p=.0001). A significant positive association was detected between the flowcytometry and C-reactive protein, erythrocyte sedimentation rates rheumatoid factor, Anti-CCP and the number of affected joints. Conclusion: CX3CR1 is a valuable biomarker of RA activity with a significant role in the local joint inflammatory reaction sparing other body parts.