Objective To study the in vivo infection model of young SD rats induced by coxsackievirus B3 (CVB3) at various concentrations and to study the distribution of the virus in host tissue, the response of the immune system to the virus, and the response of inflammatory factors, which contribute will understand the immunopathological mechanism of a viral infection. Providing an experimental basis for drug screening and efficacy evaluation. Methods Different doses of CVB3 (TCID₅₀=10_-3.34^/100 μL) were injected peritoneally in 10-day-old juvenile SD rats. Flow cytometry was used to detect the proportion of lymphocyte subsets (CD4₊^{, CD8₊}) in whole blood of D4 and D8 models, respectively. Real-time q-PCR was used to detect CVB3 load in heart, liver, spleen, lung, brain, kidney and gastrointestinal tract, and rat ELISA kit was used to detect the levels of TNF-α and IFN-γ, and HE staining was used to observe the himorphologic changes. Results Juvenile SD rats were infected with different doses of CVB3 by intraperitoneal injection, and juvenile rats in each group showed different degrees of diarrhea, and the body weight was significantly reduced .The proportion of CD8₊ ^{lymphocytes in whole blood of} juvenile rats in the stock solution group increased and the ratio of CD4₊^/CD8₊ ^{lymphocytes decreased}(P＜0.05,P＜0.01). No CVB3 was detected in the heart, liver, spleen, brain and kidney of juvenile rats in the stock solution group by real-time q-PCR. However, a small amount of CVB3 was detected in the stomach and small intestine, and a large amount of CBV3 was detected in the large intestine, with high expression of TNF-α and low expression of IFN-γ in the large intestine(P＜0.05,P＜0.01), and microscopic observation showed edema and inflammatory cell infiltration in the submucosa of the colon, cecum and rectum. The proportion of lymphocyte subsets in whole blood, the amount of CVB3 in tissues, the contents of TNF-α, IFN-γ and morphological changes in groups 10_-1^{, 10}_-2 ^{and 10_-3} were not significantly different from those in normal groups(P＞0.05). Conclusion Different doses of CVB3 induced an infectious model of young SD rats, in which crude liquid CVB3 could cause pathological changes in the large intestine (cecum and rectum), massive viral replication, inflammatory factor levels and immune cell diseases young rats, but did not cause heart, liver, kidney, lung and brain tissue lesions. It is suggested that CVB3 virus has a specific pathogenic mechanism in young rats, and more attention should be paid to virus-host interaction and virus targeting in future studies.