Objective: Leptin, the obese (ob) gene product, is a 16 kDa peptide hormone secreted mainly from white adipose tissue; acting on a receptor site in the hypothalamus to inhibit food intake and stimulate energy expenditure. Leptin levels are consistently associated with body adiposity and body mass index. In type 2 diabetes mellitus (DM), hyperinsulinemia has been reported to associate with elevated leptin levels independently of body fat mass. A common G-2548A polymorphism in the 5' region of the leptin gene was reported to have a strong influence on leptin gene expression and adipose tissue secretion. Thus, in this study, the influence of the LEP G-2548A polymorphism on plasma leptin in type 2 DM patients was evaluated. Materials and Methods: Fifty patients with type 2 DM and 50 healthy controls were screened for the presence of G-2548A polymorphism using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. Body mass index, fasting leptin and fasting glucose were also determined. Results: In the type 2 DM patients, AA genotype frequency (34%) and GG genotype frequency (26%) was higher than in normal controls (26% and 10%, respectively). Logistic regression analysis showed that LEP -2548GG genotype presented an increased risk of type 2 DM (p=0.017, OR=4.160, 95CI=1.287-13.444), after adjusting for age and gender. The association analysis showed that subjects homozygous for LEP -2548GG had higher serum leptin levels, as compared with carriers of A allele (23.8 ± 17.2 ng/ml vs 14.9 ±14.3 ng/ml, p=0.02). Conclusion: In this study, we reported association between the LEP G-2548A polymorphism in the leptine gene and type 2 DM. furthermore, significant association between the LEP-2548GG carrier status and higher leptin levels was identified. Many study have shown that leptin levels were elevated in diabetic patients. On the other hand, the G-2548A LEP variant has previously been shown to be associated with variations in serum leptin levels. Our results showed that LEP G-2548A polymorphisms is associated with higher leptin levels and increased risk for type 2 DM. Thus, the leptin gene polymorphism may be act as a molecular marker for type 2 DM risk.