Diabetes mellitus is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effect of 18β-glycyrrhetinic acid on plasma glucose and plasma and tissue lipid profiles in streptozotocin-induced diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180–200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. Rats were randomly divided into seven groups. Group I: control animals (normal, nondiabetic animals), Group II: 18β-glycyrrhetinic acid control, Group III: streptozotocin-diabetic, untreated animals; Groups IV, V and VI: streptozotocin-diabetic animals given 50, 100 and 200 mg 18β-glycyrrhetinic acid, and Group VII: streptozotocin-diabetic animals given glibenclamide. The levels of total cholesterol, triglycerides, free fatty acids, and phospholipids, were assayed in the plasma besides lipoprotein-cholesterol (high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C)) and tissues (liver, kidney and heart). Total cholesterol, triglyceride, free fatty acid, and phospholipid (LDL-C and VLDL-C in plasma only) levels increased in plasma and tissues significantly, while plasma HDL-cholesterol significantly decreased in diabetic rats. Treatment with 18β-glycyrrhetinic acid prevented the above changes and improved towards normalcy. Thus administration of 18β-glycyrrhetinic acid is able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.