Dry eye syndrome (DES) is a range of ophthalmic conditions characterized by compromised tear film homeostasis, resulting from various pathological factors and primarily manifesting as ocular discomfort and impaired ocular surface integrity. With the rise in screen time due to modern lifestyles, the prevalence of DES is increasing annually, posing a significant global public health challenge. Pathophysiologically, DES involves damage to the lacrimal functional unit (LFU), including the lacrimal glands, meibomian glands, and corneoconjunctival epithelium, highlighting its multifactorial etiology. Current treatments mainly focus on artificial tears for moisture replacement and anti-inflammatory therapies, but both are limited. Consequently, animal models are crucial for understanding the complex pathological mechanisms of DES and identifying potential therapeutic agents. Rodent eyes, with their structural and physiological similarities to human eyes and cost-effectiveness, have become widely used in DES research. This manuscript reviews the current understanding of DES pathogenesis and rodent models, discussing their strengths, weaknesses, and relevant genetic models. The aim is to furnish critical insights and provide a scholarly resource to propel future investigative endeavors into the pathogenesis of and therapy for DES.Copyright © 2025 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.