In this study, we aimed to mimic the T2DM condition in a mouse model by providing mice with a high-fat diet (HFD) and administering streptozotocin (STZ) to evaluate the morphological alterations and expression of P2X7R and P2X4R in the submandibular glands (SMGs). The gene discussed is P2RX4; the disease is type 2 diabetes mellitus.