Lacrimal fluid (tears) is important for preservation of the ocular surface, and thus dry eye induced by lacrimal hyposecretion in Sjögren's syndrome (SS) leads to reduced quality of life. However, the cause of lacrimal hyposecretion remains unknown, even though many studies have been conducted from the perspective of inflammation. Here, we hypothesized that a non-inflammatory factor induces lacrimal hyposecretion in SS pathophysiology. To elucidate such a factor, we conducted transcriptome analysis of the lacrimal glands in male non-obese diabetic (NOD) mice as a SS model. The result revealed that only four genes, including arginase 1, were downregulated in the lacrimal glands of male NOD mice after onset of lacrimal hyposecretion and dacryoadenitis. Furthermore, non-dacryoadenitis-type NOD mice were used to investigate the relationships among arginase 1 expression, lacrimal hyposecretion and dacryoadenitis. Non-dacryoadenitis-type NOD mice showed reduced tear secretion and low expression level of arginase 1. In addition, in BALB/c mice, an arginase 1 inhibitor reduced tear secretion. In conclusion, a non-inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. These results shed light on the pathophysiological role of arginase 1 in SS (dry eye).