Abstract: Objective To study the effects of TNFa on activity of TPK（tyrosine protein kinase） of the membrane insulin receptor of the muscle and liver in KM mouse. Methods Eighty KM mouse were divided randomly to the TH group（TNFa high-dose group）, TL group（TNFa low-dose group）, T1 group（TNFa once-dose group） and C group（control group）.The activity of TPK of the membrane insulin receptor in the muscle and liver without and with insulin-stimulated in all groups were observed. Results l）The activity of the TPK of the membrane insulin receptor in the muscle and liver without insulin-stimulated of TH and TL group were both lower significantly than that of C group, and TH group were lower than that of TL group.2） The changes of activity of the TPK of the membrane insulin receptor in the muscle and liver caused by insulin-stimulated of TH and TL group were both lower significantly than that of C group,and TH group were lower than that of TL group. 3）There were no significant difference of TPK of the membrane insulin receptor in the muscle and liver of the T1 group and C group. Conclusion TNFa can suppress the activity of TPK of the membrane insulin receptor in muscle and liver, and the effects of TNFa depends on the dose and time of TNFa treatment.