To seek a better pathway and proper number of parasites for Blastocystis hominis (B.h) infection in normal and immunocompromised ICR mice.(1) 10(4), 10(5) and 10(6) B.h, cultured in RPMI 1640 medium from 3 generations were used to infect mice through oral and rectum; (2) 10(6) B.h were used to infect immunocompromised mice through rectum. The reproduction of B.h in gastrointestinal tract and the pathologic changes in the tissues were observed.Mice were infected by B.h through either oral or rectum. The infected immunocompromised mice showed slow locomotion, depressed, lethargy, and descended body weight. Some infected mice discharged mucus feces, a few of them died during the experiment. Parasites were found in the whole gastrointestinal tract. Severe edema, hyperemia and congestion were observed in the tissues of jejunum, ileum, cecum and colon. The epithelia of small intestine and colonic mucous membrane showed exfoliation, inflammatory cell infiltration in submucosa, and structural changes in glands.Mice were more susceptible to Blastocystis hominis infection through rectum than orally. The parasites can be found in the whole gastrointestinal tract of mice, and can breed rapidly and cause significant pathological change in the gastrointestinal mucosa in immunocompromised mice.