• Chronic psychosocial stress disrupts the circadian transcriptome of the lacrimal gland, affecting immune cell trafficking, secretion, and lipid deposition.
• Both high platform and restraint stress models significantly reduce stimulated tear secretion and immune cell recruitment to the lacrimal gland.
• Beta-adrenergic receptor blockers and glucocorticoid synthesis inhibitors reverse stress-induced secretory and histopathological changes.
• Findings highlight potential therapeutic targets for dry eye disease in patients with psychological stress.