Abstract: Objective To investigate the role of nucleotide binding oligomerization domain(NOD)receptor in insulin resistance of skeletal muscle in different obesity susceptible rats induced by high fat diet.Methods Male Sprague-Dawley(SD)rats were randomly divided into control group and high fat group fed with normal and high-fat diet,respectively.The rats in high fat group were subdivided into obesity-prone(OP)group and obesity-resistant(OR)group at 8th week.Oral glucose tolerance test(OGTT)was performed at 19th week and all the rats were sacrificed at 20th week.Lee's index,fat content and homeostasis model assessment of insulin resistance(HOMA-IR)were measured.Glucose transporter 4(GLUT4),NOD1 and NOD2 mRNA expression were determined with real-time PCR.Results Body weight,fat content,fasting insulin level and HOMA-IR in rats of OP group were higher than control and OR group(P<0.01).Though there was no difference in body weight between rats in OR and control group,OR group showed higher Lee's index,fat content and HOMA-IR compared with those of the control group(P<0.01 or P<0.05).Expression of GLUT4 mRNA in rat skeletal muscle of OP group was down-regulated and NOD2 mRNA was significantly up-regulated than those of the control and OR group(P<0.01 or P<0.05).Conclusion High fat diet might be a NOD2 activator in rat skeletal muscle and play an important role in skeletal muscle insulin resistance.