OBJECTIVE: Obesity plays a central role in the insulin resistance syndrome, which is associated with hyperinsulinemia, hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of atherosclerotic cardiovascular disease. The present study was done to assess the effect of Gymnema sylvestre extract (GSE) in the high fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. MATERIALS AND METHODS: Adult male Wistar rats (150-200 g body weight) were used in this study. HFD was used to induce obesity. Body mass index, hemodynamic parameters, serum leptin, insulin, glucose, lipids, apolipoprotein levels, myocardial apoptosis, and antioxidant enzymes were assessed. Organ and visceral fat pad weights and histopathological studies were also carried out. RESULTS: Oral feeding of HFD (20 g/day) for a period of 28 days resulted in a significant increase in body mass index, organ weights, visceral fat pad weight, cardiac caspase-3, cardiac DNA laddering (indicating apoptotic inter-nucleosomal DNA fragment), and lipid peroxide levels of cardiac tissues of rats. Further, mean arterial blood pressure, heart rate, serum leptin, insulin, LDH, LDL-C, total cholesterol, triglycerides, and apolipoprotein-B levels were enhanced significantly, whereas serum HDL-C, apoliporotein-A1 levels, and cardiac Na(+) K(+) ATPase, antioxidant enzymes levels were significantly decreased. Furthermore, treatment with standardized ethanolic GSE (200 m/kg/p.o.) for a period of 28 days resulted in significant reversal of above mentioned changes in the obese Wistar rats. CONCLUSION: The present study has demonstrated the significant antiobesity potential of GSE in murine model of obesity.