Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized ‎by loss of self-tolerance causing immune-mediated tissue destruction and various clinical presentations ‎Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and ‎autoimmune disorders. This study investigates polymorphisms of the IL-18 gene in SLE patients at positions -‎‎607 and -137 of the promoter to elucidate their possible roles in the activity and severity of this disease. Fifty ‎SLE patients and fifty unrelated healthy control group were included. All SLE patients underwent thorough ‎clinical examination and SLE disease activity assessment using SLEDAI. Genomic DNA was extracted from ‎peripheral venous blood. Sequence-specific primer PCR analysis were used to genotype the DNA samples for ‎SNP-607and SNP-137, while plasma IL-18 concentrations of patients and control subjects were measured by ‎enzyme-linked immunosorbent assay. The frequency of SNP-607/CC genotype showed significant increase ‎‎(P