Background: CD26 has a role in the pathogenesis of inflammation and participates in degrading interferon-γ-induced chemokine and inflammatory cytokines which have a role in Systemic lupus Erythematosus (SLE) pathogenesis. Objectives: This work was carried out to evaluate the level of CD26 mRNA expression in the peripheral blood leucocytes of SLE patients by quantitative RT-PCR and correlates this level with the disease activity and lupus nephritis. Methodology: thirty SLE patients' blood samples were obtained, leucocytes were isolated and the level of CD26 mRNA expression was evaluated by RT-PCR. Twenty healthy subjects matched for age and sex were chosen as a control group. All cases were subjected to full history taking, thorough clinical exanimation and laboratory investigations. The disease activity was evaluated with systemic lupus erythematosus disease activity index (SLEDAI).. Patients were subdivided into: 12 SLE patients with lupus nephritis and 18 SLE patients without lupus nephritis. Results: CD26 mRNA expression increased 1.28 fold in SLE patients compared to the controls (p<0.05) with no significant correlation between CD26 mRNA expression and SLEDAI score. No significant difference (p>0.05) was found among patients with and those without lupus nephritis. Conclusion: Our results support the hypothesis that CD26 mRNA plays a role in the pathogenesis of SLE; however it is not a good predictor of SLE disease activity or lupus nephritis.