Purpose Encephalitozoon intestinalisaffects many physiological processes of host cells to survive, proliferate, and spread to different regions within the body. In this study, the effects of the parasite on host cell apoptosis and proliferation were investigated. Methods To determine the impact of the parasite on the host cell apoptosis, changes in the expression profile of genes were investigated with the qPCR array using the Human Apoptosis Panel in infected and non-infected macrophage cells. Also, the rate of apoptosis in the cells was determined by Giemsa staining method. Cell proliferation was determined by measuring the DNA concentration in infected and non-infected cells. Results The thirty-six of apoptosis-related genes were down-regulated, while 20 of apoptosis-related genes were up-regulated in infected cells compared to uninfected cells. However, there were no significant changes detected in 32 analyzed genes between infected and control groups.E. intestinaliswas determined to decrease cell proliferation in U937 macrophage cells. Unexpectedly, Giemsa staining showed an increase in the rate of apoptosis in infected cells. Conclusion Regulated genes after infection are involved in many different biological pathways and various components of the cell. This suggests that the parasite uses highly sophisticated ways to maintain the viability of the cell.