Objective Establishing the drug-resistant Candida albicans disseminative infected mice model for new drug screening. Methods The disseminative infected mouse model was generated by intravenously injecting a clinical Drug-resistant Candida albicans strain (CaR) to immunosuppressive ICR mice. The features of model was evaluated by clinical symptom, survival condition, fungal burden in tissue, histopathology, cytokines assay and medication. Results After infected with CaR (0 day), the death of mice started at the first day, though, compared to clinical drug sensitive strain (CaS) infected group, the difference of mortality rate in 16-day observation period was not significant in two groups (CaR, 90.7%; CaS, 86.2%, P=0.158), mice in CaR group died faster than those in CaS group at the early stage; On the fourth day of infection, Candida albicans could be detected in the different tissues, and we found fungal burden in kidney and brain was a significant difference. The typical granuloma caused by fungal infection was the main histopathological feature observed in the kidney, brain and heart. Cytokines in renal tissue were detected by flow cytometry, The changes of IL-1α,IL-6,TNF-α and IFN-γ in kidney were significant. Compared with CaS group, IL-1 and IFN-γ were significantly higher and TNF-α decreased significantly in CaR group.The mice of groups CaR and CaS were treated with 10 mg/kg fluconazole, the mortality rates were 83.3% and 37.5%, which have a significant difference. Conclusions In this study, we successfully established a drug-resistant Candida albicans disseminative infected mice model which is potential tool for the development of new anti-infectious agent.