Objective: To elucidate the implications of L-carnosine on interleukin-1a (IL-1a)-induced inflammation of lacrimal glands (LGs). Materials and methods: Forty rabbits were divided equally into four groups: control group (G1), IL-1a (G2), L-carnosine (G3), and L-carnosine plus IL-1a (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED). Results: The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-c, tumor necrosis factor- a, transforming growth factor-b1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1a-induced inflammation of LGs. Conclusions: IL-1a induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED