The levels of triglyceride(TG)and free fatty acid(FFA)in serum,liver,skeletal muscle,and pancreas of lipoprotein lipase gene knockout heterozygous(LPL+/-)mice and C57 mice were determined.Intraperitoneal glucose tolerance test(IPGTT)was performed to evaluate insulin sensitivity and β-cell function.The results showed that the Iipid content in 16 weeks LPL+/- group did not increase significantly.The TG and FFA contents in 28 weeks LPL+/- group were significantly higher than those in control and 16 weeks LPL+/-group(all P<0.05).In 50 weeks LPL+/- group,FFA levels in serum and pancreas,and TG content in pancreas increased significantly compared with other three groups(all P<0.05).The IPGTT result showed that the blood glucose levels increased from 15 to 120 min,not at 0 and 5 min.The blood glucose levels during 30-120 min increased significantly in 50 weeks LPL+/- group compared with other three groups(P<0.05).Fasting insulin(FINS),homoestasis assessment of insulin resistance(HOMA-IR)and pancreatic β cell function also increased gradually with age.FINS and HOMA-IR in 28 weeks LPL+/- group were higher than those in control and 16 weeks LPL+/- group.These results suggest that LPL is a key enzyme in lipid metabolism and plays a crucial role in the development of insulin resistance and diabetes. Key words: Lipoprotein lipase; Triglyceride; Free fatty acids; Lipotoxicity; Insulin sensitivity