Objective To establish a mouse model of endogenous infection induced by intestinal disseminationand provide a reliable experimental model for studies of the mechanism of intestinal microecology and endogenous infection.Methods Twenty-four female ICR mice were randomly divided into model group A, model group B, and control group C.The mice in group A were administered a broad spectrum antibiotic solution orally to disturb the balance of normal intestinalflora, and then 5-fluorouracil was injected into the tail vein for immunosuppression. The mice in group B were administeredwith Candida albicans by gavage after the same treatment as the group A. The control group C was administered with normalsaline by the same method. Changes of fecal flora in the mice were continuously observed during the experiment. Theamount of bacteria in mouse tissues was detected by the plate counting method. Pathological changes of the lung, liver,cecum, and large intestine were observed using HE staining. Quantitative changes of intestinal flora in the mice wereobserved by quantitative PCR. Results At the end of the experiment, bacterial infection occurred in the tissues and organsof the mice in group A, and mixed bacterial and fungal infections occurred in the group B. Lung and liver histology of themice in both infection groups showed typical inflammatory manifestations, while the cecum and large intestine showedmucosal inflammation and disrupted barrier integrity. Quantitation of intestinal flora showed disruption of the main intestinalflora structure in the two model groups, and the ratio of the intestinal colonization resistance index was less than 1.Conclusions Under the conditions of intestinal flora disturbance and immune suppression, intestinal pathogenic bacteriaor opportunistic pathogenic bacteria break through the intestinal mucosa barrier and cause tissue and organ infection inmice. This model can provide a reliable basis for the studies on prevention and control of endogenous infection from the perspective of intestinal microecology.