Objective To explore the characteristics of immunological changes in tree shrews infected with orthoreovirus, and provide a theoretical basis for the prevention of virus in tree shrews. Methods 40 - 50?day?old tree shrews were divided into three groups: MRV1/ TS/2011 virus?infected and MRV3/ TS/2013 virus?infected groups, and saline?treated control group. On the 1, 8, 14, 21, and 28 days after infection, blood samples were taken from the tail vein and used for RT?PCR, flow cytometry and ELISA detection, to assess the viral load, number of CD4/ CD8/ CD19 cells, and IFN?gamma expression. Results The MRV1/ TS/2011 and MRV3/ TS/2013 viral load in the plasma and the number of CD4⁺ and CD19 ⁺ cells reached a peak at the 14th day after infection. At the first day after MRV1/ TS/2011 infection, the CD4 ⁺ cells had a significantly higher expression compared with the normal group. CD8 ⁺ cells and the IFN?gamma expression reached a peak at the 21st day after infection. The expression of CD4 ⁺ was even higher after MRV1/ TS/2011 infection, and the expression of CD8 ⁺ cells was higher after MRV3/ TS/2013 infection. Conclusions We would conclude that after MRV1/ TS/2011 and MRV3/ TS/2011 virus infection, accompanying the changes of viral load, it shows some regularity of the expression of CD4/ CD8/ CD19 and IFN?gamma in the tree shrews: at the early stage of MRV1/ TS/2011 virus infection, humoral immunity is stimulated, and CD4 ⁺ cells play a major role. MRV3/ TS/2013 virus may mainly affect the cellular immunity, while humoral immunity only plays a role at a high viral expression or the late stage of infection. CD4 ⁺ cells may be more sensitive to type 1 reovirus, and CD19 ⁺ cells may be more sensitive to type 3 reovirus.