Background: Between 20% and 40% of patients with diabetes ultimately develop diabetic nephropathy (DN), which is the most common cause of end stage renal disease requiring dialysis. Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of diabetic nephropathy. The promoter region of the human IL-18 gene has common single nucleotide polymorphisms at positions -607 and -137. These polymorphisms have been shown to regulate the IL-18 production of peripheral blood monocytes and be associated with the transcriptional activity of the IL-18 gene. Aim: The purpose of this study is to detect IL-18 (-607C/A) polymorphism, and to find its association with IL-18 and its binding protein levels in patients with diabetic nephropathy.Methods: For all subjects, the (-607C/A) gene polymorphism was detected by PCR/RFLP, while the IL-18 and IL-18BP levels were determined by ELISA.Results: There was no statistical significant difference among the studied groups as regards the percentage distribution of the genotypes and allele frequency, where the CC genotype was the most frequent genotype in the DN group. Also, there was highly significant increase in IL-18 and IL-18BP levels in DN group compared to diabetic group without nephropathy and to control group.