Purpose: To observe the histologic changes and clusterin expression in the acinar cells of the submandibular gland in streptozotocin-induced diabetic rat following irradiation. Materials and Methods: Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the Sprague-Dawley rats by injecting streptozotocin, while the control rats were injected with citrate buffer only. After 5 days, rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14,21, and 28 days after irradiation. The specimen including the submandibular gland were sectioned and observed using histologic and immunohistochemical methods. Results : Morphologic change of acinar cells was remarkable in the diabetic group, but was not observed in the diabetic-irradiated group. Necrotic tissues were observed in the diabetic-irradiated group. Coloring of toluidine blue stain was most increased at 14 days in the diabetic group, however there were no significant change throughout the period of the experiment in the diabetic-irradiated group. Expression of clusterin was most significant at 14 days in the diabetic group, but gradually decreased with time after 7 days in the diabetic-irradiated group. Degeneration of clusterin was observed in the diabetic-irradiated group. Conclusion : This experiment suggests that the acinar cells of submandibular gland in rats are physiologically apoptosed by the induction of diabetes, but that the apoptosis is inhibited and the acinar cells necrotized after irradiation.