Aim of the Work: The present study attempted to assess the level of serum calprotectin CLP in patients with rheumatoid arthritis as well as its correlation with clinical, laboratory radiological and ultrasonographic parameters of disease activity and severity. Patients and Methods: 40 RA patients treated with conventional DMARDS were enrolled as a study group and 40 age and sex matched healthy participants, as a control group. ELISA was used to measure serum calprotectin (CLP) levels, while (Anti-CCP), (CRP), (ESR), and (RF) were also measured. The disease activity was evaluated using the DAS28, the disease severity by Rheumatoid arthritis Severity Scale (RASS). Affected joints were sonographically assessed. Plain x-ray of wrists as well as hands were evaluated using the modified Larsen score (MLS). Results: The level of serum CLP was remarkably higher in RA patients treated with conventional DMARDS compared to controls (P<0.001). There was a significant positive association between serum CLP level in patients with RA and DAS28, CRP, ESR, RF, RASS, MLS Anti-CCP as well as ultrasonographic findings. Relation between patient's results and types of graft used showed no statistically significant differences between them. Conclusion: The CPL is incremented in the cases with RA, it correlates with activity and severity and may be a candidate for biomarker.