Objective: Metabolic syndrome is affected by the interaction of multiple genes and diverse environmental factors. Among environmental factors, food composition is a major one in modulating the development of metabolic diseases. Using diabetic hamster model, in the present study, we investigated the effects of different n-3 fatty acids diet (n-3 PUFAs) on metabolic disease. Methods: 40 healthy male depuratory hamsters were divided into 4 groups: control group (10% lard), aerobic exercise (EX) group (10% lard), high alpha-linolenic acid (HALA) group (n6/n3, 12.4:1) and low alpha-linolenic acid (LALA) group (n6/n3, 18.4:1). 10 weeks later, the hamsters were fasted for 12 hours and then anaesthetized. After blood samples were collected from femoral artery, all animals were sacrificed, and tissue samples, including the internal organs, skeletal muscles as well as amphi-organs adipose, were harvested. Serum glucose, insulin and lipids were determined. The levels of free fatty acids (FFA), and triacylglycerol (TG) in serum and tissues were also measured. Hepatic lipase (HL) and lipoprotein lipase (LPL) were determined in the tissues of liver, skeletal muscle and adipose. Furthermore, we measured the levels of leptin and TNF-alpha in adipose tissue, PPARs in liver by RT-PCR. Results: N-3 PUFAs did not affect body weight gain induced by high-fat food. However, it significantly reduced the mass of intermuscular adipose, not other fat tissues. More importantly, n-3 fatty acid dramatic decreased the fasting glucose (FPG) and fasting insulin (FINS), alleviating insulin resistance index (HOMA-IR). We further found that, after supplementation with n-3 PUFAs, hepatic LPL dramatically elevated. PPARs, including PPAR-alpha, gamma and delta, significantly increased in n-3 PUFAs groups, especially in HALA group. Conclusion: N-3 fatty acids is able to reduce body fat masses and improve insulin resistance (IR) possibly through increasing hepatic LPL and elevating the expression levels as well as activity of PPARs. Supplement of n-3 fatty acids in dietary might help prevent diseases associated with metabolic syndrome, including diabetes, coronary heart disease, stroke etc.