Staff at a university laboratory responsible for management of a captive insurance colony of endangered Amargosa voles (Microtus californicus scirpensis) discovered an outbreak of tropical rat mites (Ornithonyssus bacoti) infesting 106 voles. This bloodsucking mesostigmatid mite typically occurs in laboratory settings and can cause weight loss, wounds, or other negative impacts on health. The source of the infestation was likely feral rodents, and the route was suspected to be straw bedding. Twenty-nine of the 106 (27.4%) infested voles developed ulcerated dorsal skin lesions that resolved when treated with topical selamectin. A triad approach was implemented to eradicate the mites, consisting of environmental management, individual animal treatment, and training. Voles were moved individually into a clean room containing only autoclaved materials (including straw), cages were treated with permethrin-impregnated cotton, treatment order was instituted to avoid transferring mites, and voles coming from outside were quarantined. All animals in an infested room were treated with topical selamectin, and personnel were trained on risks and new procedures. No adverse effects from the use of selamectin were identified, and this efficient protocol does not require the long-term use of acaricides. This report documents infestation of an endangered rodent with an exotic parasite, safe use of permethrin and selamectin in this species, and comprehensive management to manage a large infestation.