Chronic kidney disease (CKD) is a progressive, irreversible process. The precise aetiology is often uncertain, but diabetes is the commonest cause of established renal failure (ESRF) in those starting dialysis.The aim of the present study was to detect the prevalence of endothelial nitric oxide synthase (eNOS) genetic polymorphisms [the 27-bp repeat in intron 4 and the G-894T polymorphism in exon 7] among ESRD Egyptian patients and to study the influence of these genetic polymorphisms on progression of the disease and on the clinical and laboratory features of these patients. To achieve our aim, genotyping for the intron 4 a/b polymorphisms for the eNOS gene was performed by PCR amplification of the target genes while genotyping of the G-894Tpolymorpism, was performed by PCR amplification of the target genes followed by allele specific restriction enzyme digestion (PCR-RFLP).The present study included 35 ESRD patients and 20 healthy volunteers who were age, sex, and ethnically matched as control group.In this study, we concluded the following, ESRD patients had a significantly higher frequency of eNOS 4 a/a and b/a genotypes (mutant) than the control group. The presence of eNOS 4a allele was significantly higher in patients than the control group. In addition, the frequencies of the G-894T mutation (GT) as well as the T allele frequency in ESRD patients were significantly higher than the control group. Also in this study there was a statistically significance difference between the frequencies of the wild genotypes (bb) and the polymorphic genotypes (a/b) in ESRD patients presenting with diabetes and healthy controls. These results suggest that the eNOS gene polymorphisms are genetic risk factors and may serve as a useful genetic marker of susceptibility to chronic renal failure.