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Objective: To evaluate the effect of pomegranate peel extract with or without rosiglitazone on plasma glucose and lipid profile in insulin resistant diabetic rats. Study Design: Randomized controlled trial. Place and Duration of Study: Department of Physiology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health (N.I.H), Islamabad from 1st January 2011 to 28th May 2011. Material and Methods: Type 2 diabetes mellitus was induced in sixty healthy rats. The diabetic rats were divided into four groups, namely diabetic control group which received intraperitoneal injection of normal saline daily, pomegranate group which was treated similar to control group and also received pomegranate peel extract (200mg/kg body weight) orally once daily, rosiglitazone group which received intraperitoneal injection of rosiglitazone (5mg/kg body weight) daily and the combined group received both pomegranate extract (100 mg/kg body weight, orally) and intraperitoneal injection of rosiglitazone (2.5 mg/kg body weight) daily for 28 days. After four weeks of treatment, terminal intracardiac sampling was done to measure plasma glucose and lipid profile. Results: The plasma glucose and mean serum levels of cholesterol, triglyceride, low density lipoproteins and very low density lipoproteins was significantly reduced (p<0.001) in pomegranate, rosiglitazone and combined groups respectively as compared to the diabetic control. The mean serum levels of high density lipoproteins were significantly (p<0.001) elevated in above mentioned groups as compared to the diabetic control. Conclusion: Pomegranate peel extract is hypoglycemic and hypolipidemic agent in low doses when used alone or in combination with rosiglitazone in type 2 diabetic rats. [ABSTRACT FROM AUTHOR]