Objective: The objective of this study was to observe the effect of Bushen Qingre Yuyin Decoction on the spleen index, submandibular gland index, salivary secretion, submandibular gland morphology, and aquaporin 5 (AQP5) expression levels in the submandibular gland. Materials and Methods: Fifty 8-week-old nonobese diabetic (NOD) female mice were randomly divided into the following five groups: model; hydroxychloroquine; and high-, medium-, and low-dose Bushen Qingre Yuyin Decoction prescription. The blank group consisted of ten 8-week-old Balb/C rats. Bushen Yuyin Qingre Decoction was administered by gavage at 20, 40, and 80 g/kg in the low-, medium-, and high-dose groups, respectively. The hydroxychloroquine group was administered hydroxychloroquine at a dose of 80 mg/kg by gavage. The normal and model groups were administered the same amount of saline. After the different administrations, the amount of salivary secretion in the mice was regularly observed. After 12 weeks, the mice were sacrificed, and their submandibular gland tissues were excised, stained with hematoxylin-eosin, and pathologically scored. AQP5 expression levels in the tissues were detected using real-time polymerase chain reaction. Results: The spleen index of mice in the high-dose group was higher than that in the model group (P < 0.05), and the submandibular gland index of the hydroxychloroquine group and all the Bushen Qingre Yuyin Decoction prescription groups was higher than that in the model group (P < 0.05). After 6 weeks, the salivary volume of the hydroxychloroquine group and all the Bushen Qingre Yuyin Decoction prescription groups was significantly higher than that of the model group (P < 0.05); the amount of lymphocyte infiltration in mice among each administration group was significantly reduced (P < 0.05); and the AQP5 expression levels in the submandibular glands of mice had significantly increased in the hydroxychloroquine and high-dose groups (P < 0.05), with the high-dose group showing the best effect. Conclusion: Bushen Qingre Yuyin Decoction can effectively increase the spleen and submandibular gland indexes of NOD mice, increase the amount of salivary secretion, reduce lymphocyte infiltration in submandibular gland tissue, and significantly increase AQP5 expression levels, which may be positively correlated with the administered dose.