Abstract: AIM:To study the effects of NRAi-mediated gene silencing of SOCS3 on metabolic disturbance in high-fat diet rats.METHODS:F0rty five 6-week-old healthy Sprague-Dawley(SD)rats were adopted to Our research and divided into 3 groups randomly.In the standard control group(n=15),the control lenti were stereotaxieally injected into the hypothalamus of rats which then fed with standard chow:In the high-fat diet control group (n=15),the control lenti were stereotaxically injected into the hypothalamus of rats which then fed with high-fat diet;In experimentgroup(n=15),the SOCS3 lenti were stereotaxically injected into the hypothalamus of rats which then fed with high-fat diet.Animal weight was measured weekly.Up to 8 weeks after treatment,before exeduted,fasting plasma slueose Was measured, After exeduted,serum was collected for measurement of serum leptin,insulin,triglyceride,total cholesterol.RESULTS:The experiment group rats gained smaller weight,lower triglyceride and total cholesterol than hish-fat control group rats(P<0.01)and showed larger weight,higher triglycefide and total cholesterol than CS rats (P<0.05).Levels of serum leptin and insulin were lower in experiment group rats than high-fat control group rats(P<0.01).There were no significant differences in comparison of levels serum leptin and insulin in experiment group rats with the standard control group rats.CONCLUSION:Body weight,serum leptin,insulin,triglyceride and total cholesterol concentration were decreased through down-regulation of SOCS3 expression by RNAimediated gene silencing of SOCS3,suggesting that down-regulation of SOCS3 expression is a promising therapeutic approach in obesity,diabetes and chronic complications.