Background: Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin gene could be responsible for obesity and insulin resistance in some individuals. The aim of this study is to elucidate the association of Leu72Met polymorphism in preproghrelin gene with obesity and type 2 diabetes mellitus.Methods: The current study was conducted on 70 non pregnant females ranging in age from 30-50 years old. They were divided into 3 groups: 20 lean non-diabetic females (BMI <25 kg/m2 ), 20 (Ob/Ow) non-diabetic females ( BMI > 25 kg/m2) and 30 lean diabetic females ( BMI <25 kg/m2). They were investigates for; fasting plasma glucose level, Glycosylated heamoglobin (HbA1c), serum lipid profile and DNA analysis (The Leu72Met polymorphism of the Ghrelin gene was screened using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique (PCR-RFLP).Results: There was no statistical significant difference of the Leu72Met polymorphism of the Ghrelin gene with Obesity and Type 2 Diabetes. Leu/Met genotype was more prevalent among Obese/Overweight. In individuals with Leu/Met genotype Total cholesterol and LDL tend to be higher in individuals with Type 2 Diabetes, T.G. level tend to be higher in Obese/Overweight individuals.