Glaucoma is a generic term for an etiologically heterogeneous but clinically similar dysfunction and death of retinal ganglion cells (RGCs) often associated with elevated intra ocular pressure. It is the leading neurodegenerative cause of blindness and the second leading cause of blindness worldwide after cataract.Primary Open Angle Glaucoma (POAG) is a glaucoma with a visually open anterior chamber angle or drain (by gonioscopy), and without underlying secondary ocular disease. POAG is the most common of the glaucomas, accounting for up to 75% of all glaucoma.The gene encoding eNOS (endothelial Nitric Oxide Synthase) is located on chromosome 7q35-36. It has been established that the VNTR (variable number tandem repeat) in the intron 4 of eNOS significantly influences the plasma NO levels. Retinal ganglion cell (RGC) degeneration in the glaucomatous optic nerve head of POAG patients clearly corresponds to excess plasma NO-mediated neurotoxicity. In the current study, there is no significant association between eNOS 27 bp VNTR polymorphism which located in intron 4 and POAG in the Egyptian patients (p=0.139). However by exclusion of DM from the cases and the controls, we found a significant increase in bb genotype in the control group compared to glaucoma group (p=0.04). Also there was a significant increase in b allele in non diabetic control subjects compared to non diabetic glaucomatous patients (p=0.036).