OBJECTIVETo observe the effect of Yangfei Ziyin Decoction (YZD) on symptoms, serum levels of TNF-alpha, IL-6, and aquaporin-5 (AQP-5), and pathology of Sj6gren's syndrome (SS) model mice.METHODSTotally 60 mice were divided into 6 groups according to random digit table, i.e., the model group, the normal control group, the high, medium, low dose YZD groups (administered with YZD at 36.7, 18.4, 9.2 g/kg, 0.2 mL/10 g), the Chinese patent medicine group [CPM, administered with total glucosides of paeony at 0.6 g/kg], 10 mice in each group. All intervention was performed for six successive days in a week, with an interval of one day, a total of 50 days. Body weight, salivary secretion, food and water intake were measured at day10, 20, 30, 40, and 50, respectively. At day 50 blood was collected. Submandibular gland, thymus, and spleen were weighed. Serum levels of TNF-alpha, IL-6, and AQP-5 were detected by ELISA. Pathological changes of submandibular gland were observed. Results Compared with the normal control group, there was no change in water intake of mice in the model group, but with reduced salivary secretion (P < 0.01, P < 0.05). Thymus/spleen/submandibular gland weight and index increased in the model group (P < 0.01, P < 0.05). Compared with the model group at the same time point, salivary secretion increased in the CPM group and 3 YZD groups (P < 0.01 , P < 0.05). Compared with the model group, thymus/spleen/submandibular gland weight and index decreased in the CPM group (P < 0.01, P < 0.05). Thymus/submandibular gland weight and index decreased in the low dose YZD group (P < 0.01, P < 0.05). Thymus/submandibular gland weight and index, and spleen index decreased in high and medium dose YZD groups (P < 0.01 , P < 0.05). Levels of TNF-alpha and IL-6 decreased, but AQP-5 level increased in the CPM group (P < 0.05). AQP-5 level increased in high and medium dose YZD groups (P < 0.01 , P < 0.05). In the model group alveoli and duct of salivary gland were destroyed, alveoli and duct were irregular, epithelial cells were degenerated, necrotic, and desquamated. Mild-to-moderate lymphocytic infiltration occurred around submandibular gland. Pathological changes were alleviated in the CPM group and 3 YZD groups.CONCLUSIONYZD could improve clinical symptoms, serum levels of TNF-alpha, IL-6, AQP-5, and pathological changes of SS model mice.