Objective:To investigate the protective effect of Zengye Decoction(增液汤,ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.Methods:Twenty-seven female NOD mice were randomly equally divided int0 3 groups:the model group,the hydroxychloroquine (HCQ) group,and the ZYD group.Nine C57/B6 mice served as the normal group.After 1-week acclimation,the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD,respectively,and the normal and model groups were administered with normal saline.Changes in the salivary flow rate were observed.Mice from all 4 groups were sacrificed at the age of 20 weeks.The serum and SMGs were collected.Serum cytokines gamma-interferon (IFN-γ),interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay.Histological changes in the submandibular glands were examined by hematoxylin and eosin staining.The mRNA expression of IFN-γ,IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction.Results:Compared with the model group,the salivary flow of the ZYD group significantly increased (P＜0.05),the extent of the histological changes was ameliorated (P＜0.05),and the Th1/Th2 cytokine imbalance was remedied (P＜0.05).In the ZYD-treated mice,the VIP mRNA was up-regulated (P＜0.05).Conclusions:ZYD is beneficial in protecting structure and function of SMGs in NOD mice.The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance,and with the prevention of a progressive decline of the VIP level.