Background/Aim: Tears secreted from the lacrimal gland are essential for preserving the ocular surface. Thus, dysfunction of the lacrimal gland in Sjögren's syndrome (SS) can lead to dry eye, resulting in a reduced quality of life. We previously reported that blueberry 'leaf ' water extract prevents lacrimal hyposecretion in male non-obese diabetic (NOD) mice in a SS-like model. In this study, we investigated the effect of blueberry 'stem' water extract (BStEx) on lacrimal hyposecretion in NOD mice. Materials and Methods: Male NOD mice were fed 1% BStEx or control (AIN-93G) for 2, 4, or 6 weeks from 4 weeks of age. Pilocarpine-induced tear secretion was measured using a phenol red-impregnated thread. The lacrimal glands were histologically evaluated by HE staining. Inflammatory cytokine levels in the lacrimal glands were measured using ELISA. Immunostaining was performed to examine aquaporin 5 (AQP5) localization. The expression levels of autophagy-related proteins, AQP5, and phosphorylated AMPK were measured using western blotting. Results: After feeding BStEx to mice for 4 or 6 weeks, tear volume was observed to have increased in the BStEx group compared with that in the control group. There were no significant differences in inflammatory cell infiltration, autophagy-related protein expression, or the localization and expression of AQP5 in the lacrimal glands between the two groups. In contrast, AMPK phosphorylation increased in the BStEx group. Conclusion: BStEx prevented lacrimal hyposecretion in the SS-like model of male NOD mice, probably by opening tight junctions via the activation of AMPK in lacrimal acinar cells.Tears secreted from the lacrimal gland are essential for preserving the ocular surface because of their physiological functions of wetting the cornea and sclera, providing oxygen and nutrition, and protecting against bacteria and foreign substances. Tears are also necessary for clear vision because light must be correctly refracted through tears. Thus, dysfunction of the lacrimal gland can lead to a reduced number of tears and, in turn, dry eye, resulting in a reduced quality of life. There are several causes of lacrimal dysfunction, including Sjögren's syndrome (SS) (1), radiotherapy for head and neck tumors (2), and metabolic syndrome (3). In addition, the increased amount of time spent working with visual display terminals, such as computers and smartphones, has the potential to cause lacrimal dysfunction and dry eye (4, 5).Primary SS is an autoimmune disease accompanied by the infiltration of inflammatory cells into exocrine glands, such as 1003