Background: Two thirds of the world's populations live in countries where obesity-related illness is a significant cause of death. There is a considerable increase in adult obesity and there is good evidence that more children are also becoming obese especially over the last 30 years period. Objective: To assess A803G polymorphism in the NAT2 gene in Egyptian obese children and adolescents and to detect the relation between this gene mutation and development of impaired glucose homeostasis in them. Patients and methods: 100 children and Adolescents were investigated in the study. They were divided into 2 groups according to their HbA1c: 50diagnosed as pre-diabetic obese were enrolled as group (1) and 50 diagnosed as non-diabetic obese were enrolled as group (2). Results: correlation between HbA1c and HOMAIR showed that HbA1c was statistically significantly positively correlated with weight, waist circumference, systolic and diastolic blood pressures, HOMAIR, total cholesterol and LDL. While, HbA1c was statistically significantly negatively correlated with HDL and BMI-SDS, with no statistically significant correlations with other variables among Group 1. HOMA-IR was statistically significantly positively correlated with weight, waist circumference and systolic and diastolic blood pressures. While, HOMAIR was statistically significantly negatively correlated with BMI-SDS among Group 1. HbA1c was statistically significantly positively correlated with weight and waist with no statistically significant correlation with other variables among Group 2. Conclusion: Egyptian obese children and adolescents who are carrying NAT2 A803 allele might be at a high risk of developing impaired glucose homeostasis and consequent increased future risk to develop diabetes mellitus type 2.