In order to establish a stable and reliable mouse model of Cryptosporidium parvum, Ix106 Cryptosporidium parvum II d subgenotypes oocysts were used to infect 3-week-old female Kunming mice. The feces of mice before and after infection were analyzed. The samples were subjected to microscopic observation and PCR detection. The regular pattern of oocyst shedding, changes in clinical symptoms, body weight, ileal tissue pathological characteristics and ileal villus index were analyzed.The results showed that Cryptosporidium parvum oocysts could be detected in feces through both morphology and molecular analysis; the weight gain of the infected group was slightly less than that of the control group during the peak period of ovulation sacs, but the overall increase trend was consistent. During the peak of oocyst shedding, the water consumption of mice decreased, the reaction were unresponsive, and their feces became thinner. After the peak period, the mental state of the mice gradually recovered. HE staining of pathological sections of the the ileum tissue of mice on the 7th day post-infection revealed that, compared with thecontrol group, Cryptosporidium parvum was present in the ileum tissue of the infected mice, and the number of goblet cells was reduced in some areas. The arrangemant of epithelial cells were slightly disordered, epithelial cells were partially shed, and a small number of inflammatory cells were seen in the mucosal layer; the length of ileal villi became significantly shorter and blunted,and the depth of crypt became shallower, but no significant changes were found in villus diameter and mucosal thickness. The above results are basically consistent with the clinical infection symptoms and pathological changes in animals, indicating that this study has established a Kunming mouse model infected by Cryptosporidium parvum II d subgenotypes for the first time. This model provides a research basis for studying the pathogenicity of Cryptosporidium parvum, the immune regulation mechanism of the host, and drugs and vaccines screeening.