Background and objective <p>Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage, and bone destruction. Several studies have shown that leptin plays an important role in the pathophysiology of RA disease. This study aimed to evaluate serum levels of leptin in RA patients receiving biologic drugs compared to RA patients managed by non-biologic drugs, and healthy individuals.</p> Methods and material <p>In this case-control study, three groups including RA patients receiving biological drugs (remission RA patients; <i>n</i> = 20), RA patients receiving DMARDs (active RA patients; <i>n</i> = 20), and healthy controls (<i>n</i> = 20) were included. Serum leptin levels and inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were measured in all participants. These measurements were subsequently compared across the three groups. Also, the correlation between leptin and inflammatory markers in each group was evaluated.</p> Results <p>In this study serum leptin levels in remission RA patients, active RA patients, and healthy individuals were 14.49 ± 6.73, 16.94 ± 7.72, and 7.59 ± 5.94, respectively. Serum leptin level was significantly higher in patients with RA compared to healthy controls. No significant difference was observed in serum leptin levels between the two groups of RA patients (<i>P</i> &lt; 0.001). There was a lost correlation between leptin and inflammatory markers in patients with active RA. However, a new correlation between leptin and inflammatory markers emerged in RA patients receiving biological drugs.</p> Conclusion <p>Our findings suggest that anti-TNF-alpha agents do not modulate serum leptin levels in RA patients. However, these agents may change a correlation between leptin and C-reactive protein (CRP) that is absent in patients with active RA.</p> Trial registration <p>Not applicable in case control study.</p>