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[Objectives] In order to clarify the difference in activation of the immune system by live or inactivated viruses after entering the body, a high-efficiency animal model was established for the evaluation of the efficacy of immune enhancers to better improve the immune efficacy of inactivated vaccines. In this experiment, the Pseudorabies virus (PRV) Bartha-K61 strain was used to establish a PRV artificial infection mouse model, and to screen the immune-related difference factor after inoculation with live or inactivated antigens. [Methods]PRV Bartha-K61 was inoculated to experimental mice in different doses and methods, and the survival rate was calculated to screen the safe dose. Mice were vaccinated with live virus or inactivated virus at a safe dose, and ELISA kits were used to detect the level of serum PRV-specific gB antibodies and the level of serum TNF-α, IL-1β, IFN-β and IL-6 of mice 7 days after immunization; inactivated PRV was used as a specific antigen to perform lymphocyte proliferation experiments and calculate the lymphocyte proliferation index(stimulation index, SI)of each group to screen the best vaccination route. [Results] 5×104 TCID50 was a safe challenge dose for 6-8 weeks mouse; subcutaneous injection was the best way of infection. Compared with the live virus and the inactivated virus group after 7 days of infection, the serum levels of TNF-α, IL-1β and IFN-β significantly increased (P<0.001, P<0.01), the levels of PRV gB IgG antibody and the lymphocyte SI in the mouse serum also significantly increased (P<0.05, P<0.001); There is no significant difference in cytokines and SI between different inactivation methods (P>0.05). [Conclusions]The experiment successfully established an artificial pseudorabies virus infection model in mice, and clarified that after live or inactivated pseudorabies virus immunized mice, there were differential immune-related factors in the early stage of the body, providing a research platform for the evaluation and screening of subsequent immunopotentiator. [ABSTRACT FROM AUTHOR]