Background leptin (LEP) and leptin receptor (LEPR) genes have been correlated to the pathophysiology of obesity, diabetes, metabolic syndrome and associated complications. LEP G2548A (rs7799039) is a single nucleotide polymorphism (SNP) in leptin gene, the association between G2548A and increased leptinemia is controversial. Aim to study the correlation between LEP G2548A and leptin resistance and their accompaniment with insulin resistance among obese Egyptians. Patients & Methods: Forty-four obese patients and 44 normal controls were included, and polymerase chain reaction restriction fragment length polymorphism method were used. Serum lipid profile, blood glucose, serum leptin and insulin were also measured. Results Statistically significant positive correlations between insulin resistance and age, diabetes mellitus, hypertension, family history of cardiac disease, hyperlipidemia, family history of obesity, BMI, serum cholesterol, serum triglycerides, serum LDL cholesterol and allele G (for all p-value =0.0001 except cardiac disease p-value =0.006 and allele G p-value=0.001) were found. The percentages of heterozygous AG and homozygous AA genotypes were statistically significantly higher among obese group than among non-obese group (52.3% and 25% vs. 18.2 and 2.3%, respectively) (p=0.001). In contrast, non-obese group showed statistically significant higher percentage of homozygous genotype GG (Wild type) in comparison to obese group (79.5% vs. 25%, respectively) which is statistically significant (p=0.001). Conclusion Current results concluded that leptin gene G2548A polymorphism could be a genetic marker of obesity in Egypt. The correlation between (SNP) in the leptin gene (G2548A) and insulin resistance among obese Egyptians would help in improving knowledge and management of obesity among Egyptian patients.