Despite the tremendous development in radiotherapy techniques, salivary glands among tissue unintentionally exposed to radiation during head and neck cancer radiotherapy due to anatomical issue. Therefore, the purpose of this study was to evaluate the histopathological consequence of gamma radiation (15 Gy) on submandibular glands as well as cytokeratin (CK) 17 and calponin expressions for deeper understanding of the mechanism of radiation –induced salivary gland injury. The rats divided into control and irradiated groups. Rats' heads in irradiated group were subjected to a single dose of gamma radiation (15Gy).  The specimens of submandibular gland were examined for the histological changes and CK 17 and calponin expression. The intensity of CK 17 expression and also the area percent of CK 17 and calponin expression were measured. Data revealed acinar cytoplasmic vacuoles, loss of architecture and shrinkage in irradiated glands. Some areas showed degranulation of granular convoluted tubules and duct degeneration. The intensity of previously mentioned changes was increased by time. The intensity of CK 17 expression rose with time for both ductal and acinar cells while the area percent of expression decreased. The area of calponin expression decreased up to seven days after radiation and then increased at fourteen days. In conclusion, the obtained results about the histological changes as well as intensity and area of CK 17 and calponin expression indicate the deleterious acute effect of single dose (15Gy) of gamma radiation on the submandibular gland parenchyma that may hinder salivary production and secretion.