Abstract India tops the list of countries with the highest number of diabetics. It represents a spectrum of conditions characterized by hyperglyceamia, with derangements in carbohydrate, lipid and protein metabolism. Cardiovascular disease, resulting from damage to large blood vessels, causes death of 50% or more of people with diabetes. Polyunsaturated fatty acids (PUFA) from marine fatty fish are known to be heart healthy constituents. PUFA are fatty acids with two or more double bonds and are generally 18-22 carbons in length. The PUFA of marine origin are usually rich in oleic, linolenic, arachidonic, eicosapentaenoic, docosahexaenoic acids. Several studies have described the beneficial effects of PUFA. In the present study we investigated the hypolipidemic effect of PUFA concentrate prepared from fish oil, in streptozotocin-induced diabetic albino rats. Adult male albino rats were divided into three groups: Group I: non-diabetic control; Group II: diabetic control; Group III: diabetic rats treated with PUFA concentrate, administered via an intragastric tube (0.6 ml/rat), at a dose of 100 mg/kg for 27 consecutive days after the induction of diabetes mellitus. Diabetes was induced by an i.p. injection with streptozotocin for groups II and III. Lipid parameters like total cholesterol, triglyceride and free fatty acids and lipoprotein lipase (LPL) activity in heart and plasma; and lipoproteins (VLDL, LDL and HDL) and creatine kinase in heart were measured. In diabetes-induced rats, heart and plasma content of lipid fractions were increased; plasma LPL activity and HDL-C were decreased; and heart LPL activity was increased and creatine kinase activity was decreased. Â The oral administration of PUFA concentrate reduced the levels of total lipid, total cholesterol and triglyceride in heart and plasma; increased HDL-C and plasma LPL activity and reduced VLDL and LDL levels in plasma; and decreased LPL activity and increased creatine kinase activity in heart of rats as compared with the diabetic control rats. Â These results suggest that the PUFA extract protected the Group III rats from the diabetes-induced alterations in the lipid metabolism. In the present study supplementation of PUFA did not alter the state of glycaemia but significantly reduced the levels of circulating lipids and lipoproteins, viz. total cholesterol, VLDL and LDL-C, triglycerides and free fatty acids in diabetic rats. Also PUFA supplemented rats have shown a significant increase in the activity of plasma LPL activity which may be responsible for the lowering of various lipid fractions in plasma as well as heart tissue. Â PUFA supplementation may have helped in lowering the circulating levels of LDL, VLDL and triglycerides by one or more of the following mechanisms, viz., a reduction in the absorption of dietary fatty acids, thereby reducing VLDL formation in the gut, enhanced plasma lipoprotein lipase activity and a reduction in the hepatic VLDL synthesis and secretion.