Objectives:The objective of this study is to develop an experimental model of hyperlipidemia and insulin resistance (IR), markers of coronary heart disease (CHD) using high fat and high sugar (HFHS) diet and to evaluate the efficacy of the model using atorvastatin, a known antihyperlipidemic drug, pioglitazone, a known insulin sensitizer, and Tinospora cordifolia (Tc), an antidiabetic plant.Materials and Methods:Following Institutional Animal Ethics Committee permission, the study was conducted in male Wistar rats (200-270 g). The model was developed using a high fat (vanaspati ghee: coconut oil, 3:1) oral diet along with 25% fructose (high sugar) added in drinking water over a period of 6 weeks. Atorvastatin (2.1 mg/kg/day), pioglitazone (2.7 mg/kg/day) and Tc (200 mg/kg/day) were administered 3 weeks after initiation of HFHS diet and continued for another 3 weeks. Parameters assessed were weight, lipid profile, fasting blood glucose, insulin, and gastric emptying. Serum malondialdehyde (MDA) and catalase were assessed as markers of oxidative stress.Results:Administration of HFHS diet demonstrated a significant increase in blood glucose, insulin, total and low density lipoprotein cholesterol and triglycerides with a decrease in high density lipoprotein cholesterol. Treatment with test drugs decreased blood sugar, insulin, lipid parameters, increased gastric emptying rate, decreased MDA levels, and catalase activity when compared to HFHS diet group, confirming the efficacy of the model. Atherogenic index of all the test drugs (0.48, 0.57, and 0.53) was significantly lower as compared to HFHS diet group (1.107).Conclusion:This study confirms the development of a diet based cost-effective and time efficient experimental model, which can be used to study two important markers of cardiovascular disease that is, hyperlipidemia and IR and to explore the efficacy of new molecules in CHD.