Vaginal Candida glabrata infections have increased significantly in recent years and are particularly common in women with uncontrolled diabetes mellitus. Efforts to understand the pathogenesis and treatment of this infection have been hindered by the lack of experimental animal models. Before onset of hyperglycemia, nonobese diabetic (NOD) mice inoculated intravaginally with clinical C. glabrata isolates were shown to support high vaginal titers of C. glabrata for > 14 days with evidence for superficial invasion of vaginal epithelial tissue. In contrast, congenic diabetic-resistant mice and mice susceptible to Candida albicans infections were significantly less susceptible to vaginal infection by C. glabrata, suggesting a potential link between the susceptibility of NOD mice to diabetes and their susceptibility to vaginal C. glabrata infections. This animal model of C. glabrata vaginitis provides a means to study the genetics and pathogenesis of C. glabrata infections and to evaluate the efficacy of antimycotic agents against C. glabrata.