Introduction and objectives: Serotonin; (5-HT) is a neurotransmitter that has major role in energy homeostasis, behavior and mood changes; thus affects the individual’s body weight and liability to obesity. 5-HT shows control over the appetite through different receptors with discrete functions. AA genotype of 5-HT2A gene promoter polymorphism was associated with increase receptor expression and binding. This study investigates the relation between the G1438A polymorphism of the 5-HT2A gene and the susceptibility to obesity. Material and Methods: 189 individuals divided according to their BMI into control group with BMI < 25 Kg/m2 and case group with BMI ≥ 25 Kg/m2. The G1438A polymorphism of the 5-HT2A gene was detected by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) of peripheral blood DNA samples. Results: Genotype frequencies for AA and GA& GG were 25% and 75% respectively in the case group compared to 52.2% and 47.8% in the control group. Carriers of GA & GG genotype were at a significant high risk of developing obesity .Moreover; the mean energy intake per day was significantly increased among carriers of GA & GG genotype compared to AA genotype. Conclusion: G allele is a risk factor for obesity.