Abstract： Objective To establish an animal model of human rotavirus(HRV)-induced diarrhea. Methods Sixty ICR suckling mice were randomly divided into two groups, and each was further divided into 3 subgroups(A, B, C for group Ⅰ, and D, E, F for group Ⅱ);group B, C, E and F were assigned as experimental groups. while group A and D were controls. Mice in group B and C were inoculated with3 × 10~5 PFU and 3×10~6 PFU HRV Wa strain fluid respectively when they were 4-day old. Mice in group E and F were inoculated with 3×10~5 PFU and 3×10~6 PFU HRV Wa strain fluid respectively when they were10-day old. The symptoms, fecal viral excretion, intestinal histopathologies and ultrastructures of animals were observed. One-way ANOVA was used to compare the differences among the groups. Results There were significant differences in the duration of diarrhea and viral excretion, jejunal villous height, the weight at d4 and d7 after inoculation among three subgroups in group Ⅰ(F=204.38, 86.60, 7.18, 18.41 and10.08, P<0.01). Diarrhea was not observed in group Ⅱ, and the differences in jejunal villous height and the weight at d4 and d7 after inoculation among three subgroups were not significant(F=0.16, 0.13 and 1.03, P>0.05). Compared with the group D, the duration of viral excretion was longer in group E and F(F=8. 34, P<0.01). Conclusion Animal model of HRV diarrhea can be established in 4-day-old ICR suckling mice infected with 3×10~6PFU HRV.