ObjectiveTo study the expression of death receptor (CD95) on the surface of peripheral blood CD4⁺T cells and the CD4⁺ T cell numbers during the acute phase in SIVmac239 virus-infected rhesus monkeys challenged by rectal (rectal infection:IR) and intravenous (intravenous infection:IV) routes, respectively.MethodsFourteen rhesus monkeys were challenged with SIVmac239 intrarectally or intravenously. Infection was determined by monitoring the viral load, CD4⁺T lymphocyte number and CD4⁺/CD8⁺ ratio. Flow cytometry analysis was used to assess the CD95 expression on the surface of CD4⁺ T cells at nine time points during the acute-phase infection. ResultsIn the intravenous infection group, CD95 expression on the CD4⁺T cells began to increase on the next day after infection, and reached the peak value on the 7th day, meanwhile the CD4⁺T lymphocyte number was declined to the lowest point. In the rectal infection group it also began to rise on the following day after infection and the CD95 expression reached the peak value at 10 days after infection, but the number of CD4⁺T cells was reduced to the lowest point until the 17th day. Compared with the intravenous infection, the peak value of CD95 expression and the lowest point of CD4⁺T cell number appeared later in the IR group, and the peak value of CD95 expression occurred a week earlier to the lowest point of CD4⁺T cells. Conclusions CD95 expression of the CD4⁺T cells is increased and the amount of CD4⁺T cells is decreased in SIVmac 239-infected rhesus monkeys challenged intrarectally or intravenously. Our results show that CD95 expressed on the surface of CD4⁺T cells vary in the SIVmac 239-infected rhesus monkeys. It may be due to the different effects of CD95 during the acute phase infection induced by different routes.