Objective To evaluate the early changes in the apparent diffusion coefficient (ADC) of the salivary glands during radiotherapy (RT) and their association with the degree of xerostomia at 6 months after RT in patients with nasopharyngeal carcinoma (NPC). Materials and Methods We enrolled 26 patients with NPC who underwent RT. Each patient underwent diffusion-weighted MRI of the salivary glands at rest and with gustatory stimulation within 1 week before RT and 2 weeks after the beginning of RT. The ADC at rest (ADC R ) and increase and increase rate with stimulation (ADC I , ADC IR ) of the submandibular and parotid glands were calculated. The differences in the variables' values between 2 weeks after the beginning of RT and baseline (ΔADC R , ΔADC I , and ΔADC IR ) were compared to the degree of xerostomia at 6 months after RT. Results The ADC R of the submandibular and parotid glands were both significantly higher at 2 weeks after the beginning of RT than found at baseline (both p < 0.01). The ADC I and ADC IR for the parotid glands were both significantly lower at 2 weeks after the beginning of RT than found at baseline (both p < 0.01). ΔADC I and ΔADC IR of the parotid glands were associated with the degree of xerostomia at 6 months after RT ( r = −0.61 and −0.72, both p < 0.01). Conclusion The ADCs of the salivary glands change early during RT. The differences in the ADC increase and increase rate of the parotid glands between 2 weeks after the beginning of RT and baseline were associated with the degree of xerostomia at 6 months after RT.