Objective:To investigate the effect of insulin and blood glucose interference on interstitial cells of Cajal(ICC) in normal and diabetes mellitus(DM) mice stomach antrum. Methods:DM model was established by intraperitoneal injection of streptozotocin(STZ) in C57/BL6 mice. A week later,all the normal and diabetic mice were randomly divided into 4 groups,group A(normal control),B(normal mice administrated with high glucose),C(diabetic mice without interference),D(diabetic mice administrated with insulin). The blood glucose of all the mice was tested once a week. Six weeks later,the level of serum insulin was detected by ELISA,the amount of ICC was detected by Flow cytometry(FCM) and the ultrastructure of ICC in stomach antrum was detected by transmission electron microscope(TEM). Results:Compared with group A,there was a transient hyperglycemia in group B after injected glucose,and blood glucose in group C was significant inceased(P < 0.05). But there was no significant difference in blood glucose level between group A and D(P > 0.05). There was no significant difference in serum insulin level between group C or D,and no significant difference between group A and B(P > 0.05).While compared with group A and B,serum insulin level in group C or D was significantly deceased(P < 0.05). Compared with the group A,ICC quantity of the stomach centrum in B,C and D was significantly deceased(P < 0.05). There was no significant difference in ICC quantity between group C and D(P > 0.05). Compared with the group A,a significant ultrastructure change of ICC in group B,C and D was detected by TEM. The abnormal ultra-structure change of ICC in group B and C were most remarkable. Conclusions:There are quantitative decline and ultrastructure changes of ICC in DM mice stomach antrum. Both transient and persistence hyperglycemia may impair the ultrastructure of ICC and may cause ICC quantitative decline. Deficient of endogenous insulin may cause ICC quantitative decline,but not impair the ultrastructure of ICC directly. Add exogenous insulin can’t prevent from the quantity decline of ICC,but can prevent the ultrastructure change of ICC by controlling hyperglycemia.