PURPOSE: To evaluate the effect of X-ray irradiation on apoptosis and change of expression of aquaporin 5 (AQP5) and transforming growth factor-beta(TGF-beta) in the rat submandibular gland (SMG). MATERIALS AND METHODS: SMGs of 120 male Sprague-Dawley rats were irradiated with a single X-ray dose (3, 10, 20, or 30 Gy). At the early and late post-irradiation phase, apoptosis was measured by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and expression of AQP5 and TGF-beta was determined by immunohistochemical staining. RESULTS: At the late post-irradiation phase, increased apoptosis was evident and marked decreases of expression of AQP5 expression by acinar cells and TGF-beta expression by ductal cells were evident. CONCLUSION: Apoptosis after X-ray irradiation develops relatively late in rat SMG. Irradiation reduces AQP5 and TGF-beta expression in different SMG cell types.