Background & objectives: Adiponectin is an abundantly expressed adipocyte–specific protein, whose level is decreased in obesity, and which appears to be a key participant in developing inflammation, insulin resistance and metabolic syndrome (MetS). We examined whether the relationship between adiponectin and leptin, insulin resistance and MetS was independent of obesity. Materials and Methods: We studied 200 subjects, with Metabolic syndrome, diagnosed by International Diabetes Federation criteria and 200 healthy control subjects, age between 25–65 years. Clinical evaluation included anthropometry, Waist circumference, Body Mass Index and waist–to–hip ratio were calculated. The blood pressure systolic and diastolic, was also measured. Circulating levels of fasting glucose, total cholestero, high–density lipoproteins, adiponectin, leptin and free fatty acids were determined. Serum leptin, adiponectin and free fatty acids were estimated by sandwich ELISA method. Results: In our study, Subjects with the MetS had lower adiponectin and higher leptin levels (P<0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with Age, BMI, WC, Waist–Hip ratio, Fasting blood sugar, Total Cholesterol, Triglycerides, High–density lipoprotein (HDL) cholesterol, Leptin, Free fatty acid and also highly significant (P<0.0001) for all variables. Conclusion: Serum concentrations of Leptin are associated with central body fat distribution. Insulin resistance and Adiponectin is associated with Dyslipidemia and these all disorders may ultimately lead to metabolic syndrome. Adiponectin, Leptin levels, Free fatty acid could be used as markers of metabolic syndrome development in adolescents. Obesity and related disturbances put these adults at a higher cardiovascular risk. Hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD.