목적: Xerostomia, caused by damaged salivary gland, is a common side effect of cancer therapies, which can significantly impact patients' quality of life. Xerostomia animal models are not well established, and the existing ones, for example, irradiation models, are not easily accessible. This study aimed to establish a reliable and easily accessible xerostomia animal model by inducing salivary gland damage in mice using pemetrexed (PMX), providing a platform for investigating mechanisms and potential treatments for xerostomia. 방법:6-week-old BALB/c mice were administered PMX intraperitoneally at 100 mg/kg for 10 dosages over 2 weeks. Salivary gland function was assessed by measuring saliva flow rates using pilocarpine stimulation. Animals were sacrificed on day 7, 14, and 21 for salivary gland extraction. Salivary gland size and weight were measured. Hematoxylin and eosin staining were performed for histological analysis of the submandibular, sublingual and parotid glands. Immunofluorescent staining of salivary acinar markers Aquaporin 5, and ductal marker Cytokeratin 7 were performed to evaluate damage in specific types of cells. 결과:PMX administration resulted in a reduction in saliva flow rates, salivary gland size and weight compared to controls, indicating a functional degeneration in the salivary gland. Hematoxylin and eosin staining revealed glandular atrophy especially in acinar cell type in the salivary glands of treated mice. Acinar marker Aquaporin 5 has more scattered expressions in the PMX treated group compared to the control, confirming the damaging effect of PMX on acinar cells seen in the histology analysis. Changes in the expression pattern of ductal marker Cytokeratin 7 were observed, indicating changes in ductal structure. Day 21 PMX treated mice retain the atrophy histology, indicating the 10 doses PMX treatment is effective in creating a xerostomia model. 결론:This study successfully established a PMX-induced xerostomia mouse model, characterized by significant salivary gland dysfunction and tissue damage. The model can be used for investigating the underlying mechanisms and testing potential therapeutic interventions. We are also trying out the regenerative effect of tonsil-derived mesenchymal stem cells generated salivary acinar spheroids with this animal model.