BACKGROUND: A compelling feature of dry eye disease is that it occurs predominantly in women. We hypothesize that this female prevalence is linked to sex-related differences in the meibomian gland (MG). This gland plays a critical role in maintaining the tear film, and its dysfunction is a major cause of dry eye disease. To understand the factors that underlie MG sexual dimorphism and promote dry eye in women, we seek to identify an optimal model for the human MG. Our goal was to determine whether a murine MG is such a model. Toward that end, we examined whether sex differences in MG gene expression are the same in BALB/c mice and humans. METHODS: Eyelid tissues were collected from humans (n = 5-7/sex) and BALB/c mice (n = 9/sex). MGs were isolated and processed for the evaluation of gene expression by using microarrays and bioinformatics software. RESULTS: Our analysis of the 500 most highly expressed genes from human and mouse MGs showed that only 24.4% were the same. Our comparison of 100 genes with the greatest sex-associated differences in human and mouse MGs demonstrated that none were the same. Sex also exerted a significant impact on numerous ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, and chromosomes, but these effects were primarily species-specific. CONCLUSIONS: Our results indicate that BALB/c mice are not optimal models for understanding sex-related differences in gene expression of the human MG.