Background: Leptin, a protein released from adipose tissue, could have significant role in pathogenesis of obesity and type 2 diabetes mellitus. Objectives: This study aimed to evaluate variations in serum leptin levels in non-obese subjects with type 2 diabetes mellitus (T2DM). Patients and Methods: We studied forty-one patients with type 2 diabetes. Fasting lipid profile, Hemoglobin A1c (HbA1c), serum leptin, insulin, and glucose levels were measured by standard methods. Results: The serum leptin level in type 2 diabetic patients (19.32 +/- 11.43 ng/mL) was significantly lower than that in non-diabetic subjects (32.16 +/- 11.02 ng/mL). Serum leptin level was strongly and positively correlated with body mass index (BMI) (r = 0.658, P < 0.0001) and calculated body fat percentage (r = 0.431, P < 0.0001) in all the study subjects with a better corrlation in the control subjcts compared to control cases (r = 0.661 for BMI and r = 0.466 for body fat). On the other hand, leptin showed a positive and significant correlation with insulin and HOMA-beta (homeostasis model assessment for beta-cell function) in both groups. Furthermore, leptin related to homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.422, P = 0.006) was observed only in T2DM subjects. Leptin showed negative correlation with waist to hip ratio in diabetic (r = -0.407, P = 0.008) and non-diabetic subjects (r = -0.318, P = 0.049). In the regression model, BMI, HOMA-beta, and gender were independent predictors of leptin in all subjects. However, in non-diabetic and diabetic subjects, beta-cell function and insulin were independent predictors, respectively (P = 0.01). Conclusions: It is speculated that lower serum leptin levels in diabetic patients may be a consequence of male gender. Moreover, results suggest that serum leptin level in women is influenced differently than that in men.