Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 04 1 28 Hamed Hosseinalizadeh Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran Khosrow Jadidi Translational Ophthalmology Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran Salman Mirzakhah Department of Biotechnology, Payame Nour University, Tehran, Iran Ruhollah Dorostkar Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Hossein Aghamollaei Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Majdedin Ghalavand Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2026 05 21 2026 08 20 Dry eye disease (DED), also known as keratoconjunctivitis sicca, is a common chronic inflammatory disease of the eyes that causes discomfort, burning, and various other symptoms. Its prevalence is increasing, and the underlying mechanisms remain unclear. It is well established that inflammation on the ocular surface (OS) triggers DED. This is indicated by elevated levels of inflammatory cytokines, such as IL-1, IL-6, and tumor necrosis factor (TNF)-α, found in the tear fluid and the epithelial layers of the cornea and conjunctiva, as well as by the infiltration of numerous inflammatory immune cells, particularly macrophages. Any disruption in the planned functional harmony between OS structural cells and resident or trafficking macrophages can impair OS health. Over the past decade, researchers have studied the diversity and role of OS macrophages in DED. The OS, like other mucosal tissues, contains a diverse population of macrophages, some of which are altered in DED. In this review, we outline the origin of macrophages in DED and describe their specific roles in relation to the main stages of this disease process. We discuss how hyperosmolarity induces pathological changes in DED and how it is related to macrophage functions. We then explain how a high-fat diet affects macrophage-related signaling pathways and thus contributes to the development of DED. Finally, we discuss how exosomes can be used in the treatment of dry eye disease. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4847 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4847/2427