Dry eye disease (DED) is one of the most common chronic multifactorial ocular surface diseases with high prevalence and complex pathogenesis. DED results in several ocular discomforts, vision fluctuation, and even potential damage of the ocular surface, bringing heavy burdens both on individuals and the society. The pathology of DED consists of tear film hyperosmolarity and immune responses on the ocular surface. Mice are widely used for developing models that simulate human DED features for investigating its pathogenesis and treatment. DED can be classified into aqueous-deficiency dry eye (ADDE) and evaporative dry eye (EDE). ADDE can be further divided into Sjögren syndrome dry eye (SSDE) and non-Sjögren syndrome dry eye (NSSDE). SSDE mouse models include natural strains, typified by non-obese diabetic (NOD) mice, and genetically engineered ones, like Aire-/- and Id3 knockout mice. Intrinsic EDE mainly refers to meibomian gland dysfunction (MGD). Eda-/- Tabby, Sod1-/-, Elovl1-/- are the most common transgenic MGD mouse models. Transgenic mouse models provide useful tools for studying the pathogenesis of DED and evaluating its novel therapies. This review compares the major transgenic dry eye mouse models and discusses their applications in DED research.