Objective To explore the effect of Telocytes (TCs) on salivary secretion of submandibular gland by imatinib mesylate’s regulation. Methods The TCs immune-labellings C-kit/CD117 and CD34 were double labelled with immunofluorescent staining technology to localize TCs in the submandibular gland of mice. The transmission electron microscopy (TEM) method was used in the present study to observe the ultrastructure of TCs and their relationship with neighboring cells in the submandibular gland of mice. The mice were divided into 5 groups：normal group（24）, 1-week, 2-week, 3-week and 4-week medicine groups（24），which were administered medicine at 80 mg/(kg·d) daily in order to study the effect of imatinib mesylate treatment on TCs function. Immunofluorescent staining technology was used to observe the change of TCs. Western blotting was used to evaluated the change of level of CD117/CD34/α-amylase（α-Amy）protein expression. Results The immunofluorescent staining showed that TCs were widely distributed in connective tissues in submandibular gland and cellular body was small with protrusions, or telopodes(Tps). Tps were connected each other and formed network-like structure, surrounding acinus and ducts. The network structure consisting of TCs protrusions in the medication groups were gradually reduced with the time of experiment. The electron microscopy observation showed that the TPs possess like-moniliform structure, connecting with adjacent tissues and being surrounded by extracellular vesicles. The number of TPs and the intracellular organelles decreased but the intracellular vesicles increased with the time of experiment. Western blotting showed that the level of CD117/CD34/α-Amy protein expression were also declined, and positively correlated with each other. Conclusion There are TCs in the submandibular gland of mice. Intervention of TCs with imatinib mesylate may reduce the salivary function of submandibular gland by affecting the structure, immunolabel and intercellular communication of TCs.