Objective · To investigate the expression level of aquaporin 5 (AQP5) in labial gland, and interleukin-21 (IL-21) and β2-microglobulin (β2-MG) in serum of patients with primary Sj?gren's syndrome (pSS) and their association with the activity of the disease. Methods · Thirty-nine patients with pSS were collected and inflammatory indicators such as erythrocyte sedimentation rate (ESR) and IgG were detected. Lip gland biopsy was performed. All specimens were divided into four groups according to Chisholm lip gland pathological classification:Ⅰ, Ⅱ, Ⅲ and Ⅳ. The expression of AQP5 in labial gland was detected by immunohistochemistry and the levels of IL-21 and β2-MG in serum were detected by ELISA. Results · As the number of lymphocytes in labial gland increased, the expression of AQP5 protein decreased. The expression of AQP5 in labial gland was negatively correlated with IL-21, β2-MG, ESR and IgG (r=-0.924, P=0.000; r=-0.366, P=0.022; r=-0.611, P=0.000; r=-0.741, P=0.000). As the number of lymphocytes in labial gland increased, the expression of IL-21 in serum increased, and there was significant difference among four grades. There was no significant difference in serum β2-MG among the groups. Conclusion · The expression of AQP5 in labial gland of patients with pSS is related to lymphocyte infiltration, and AQP5, IL-21 and β2-MG are related to disease activity, which can be used as biological markers for clinical disease evaluation.