This study was done to assess the effects of metformin and glibenclamide on serum leptin concentration in type 2 diabetic patients. The study involved 137 patients suffering from type 2 diabetes mellitus. They were divided into 3 groups. The first group involves 35 newly diagnosed diabetic patients, who did not take any hypoglycemic agents. The second group involves 52 patients on metformin monotherapy, whereas the third group involves 50 patients on glibenclamide monotherapy. Another group which involved 35 apparently healthy subjects was used as control group. These four groups were matched. age, gender, and BMI Serum glucose concentration was estimated by the enzymatic method, while serum leptin concentration was measured using ELISA kit. The results showed that serum leptin concentration was lower in metformin group than that in glibenclamide group. In addition, there was a significant correlation between serum leptin level and BMI. No correlation was found between serum leptin level and fasting serum glucose. Therefore, the results indicated that metformin, in compared with glibenclamide, can significantly reduce the serum leptin concentration in overweight diabetic patients, consequently reducing the resistance against hormone action, and improving its action, which may lead to explain the known anorexigenic effect of metformin and its ability to reduce or prevent weight gain. In conclusion, plasma leptin level can be used as an indicator for the choice of treatment in those diabetic patients.