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Objective: The aim of the present study was to investigate the relationship of the eNOS Glu298→Asp polymorphisms with impaired flow mediated dilatation (FMD) and diastolic dysfunction in Egyptian children with family history of type-2 diabetes Mellitus (DM) Materials and methods: Brachial artery FMD and echocardiographic study were performed in 80 (mean age, 11.5 ± 2.2 years) Egyptian non-diabetic offspring of patients with DM, and 80 (mean age, 10.6+2.4 years) Egyptian non-diabetic offspring of non-diabetic parents. Analysis of the endothelial nitric oxide synthase gene polymorphism using polymerase chain reaction and restriction fragment length polymorphism. for detection of different genotype variants (Glu/Glu (GG), Glu/Asp (GT) and Asp/Asp (TT) genotype).Results: Offspring of diabetic parents showed an increase in the frequency of Glu298Asp polymorphisms, significantly higher compared with controls (P<0.0001). The FMD% was significantly correlated with impaired diastolic dysfunction in offspring of diabetic patients (r=0.435 for IVRT and r=462 for E/Em). The Glu298Asp was significantly associated with impaired FMD and elevated E/Em among non-diabetic offspring of diabetic patients (P<0.001 and <0.005). Conclusion:Glu298Asp polymorphism in the endothelial nitric oxide synthase gene was significantly associated with impaired FMD and diastolic dysfunction in non-diabetic children with family history of diabetes.