This study was designed to evaluate the effect of prolonged intake of Pyruvate on insulin resistance, leptin and lipid metabolism in obesity -induced in female rats by feeding high fat diet.Fifty female albino rats were divided into five equal groups of 10 rats each. Group Ι:( Control negative group): rats fed normal diet. Group II: (Control positive group): rats fed high fat diet (HFD) and administered no drugs. Group III: rats fed HFD and administered pyruvate(270 mg/kg b.wt./day, orally)for 8 weeks. Group IV: rats received HFD and administered pyruvate (540 mg/kg b.wt./day, orally). Group V: rats received the control normal diet andadministered pyruvate once daily(540 mg/kg b.wt.,orally) for 8 weeks. Blood samples were collected at 2, 6, 8 weeks from the onset of pyruvate administration for determination of serum glucose, insulin, insulin resistance, leptin, total cholesterol(TC), triacylglycerols(TAG), phospholipids, Low density lipoprotein-cholesterol (LDL-c), Very low density lipoprotein-cholesterol (VLDL-c) and High density lipoprotein-cholesterol (HDL-c) levels in addition to serum transaminases enzymes(AST, ALT) and creatine kinase-MB (CK-MB) activities. The obtained results revealed that, rats fedHFD exhibited marked hyperglycemia, significant elevation of serum leptin, insulin and insulin resistance, AST, ALT and CK-MB,lipids profile(TC, TAG,LDL-C, VLDL-c) with marked decreased in serum HDL-c concentrations compared to rats fed normal diet. Meanwhile, administration of pyruvate to HFD-fed rats tended to prevent hyperglycemia, improve dyslipidemia and other changes relevant to cardiovascular disease mainly through improving leptin and insulin resistance. These results suggest that, pyruvate is effective in improving the obesity and its associated many important complications such as diabetes mellitus and coronary heart disease.