Abstract: In order to study the effect of porcine Pseudorabies virus（PRV） infection on pyroptosis-related factors in mouse spleen, in the experiment, 40 Balb/c mice were randomly divided into control group and test group（including 48-hour group, 72-hour group, and 96-hour group）. The mice in the test group were subcutaneously inoculated with 1×10~3 TCID₅₀/100 μL PRV 200 μL, and the mice in the control group were injected with the same volume of normal saline. The spleens of mice were collected; and the levels of interleukin-1β（IL-1β） and interleukin-18（IL-18） in spleen tissue were detected by enzyme-linked immunosorbent assay; the gene transcription and protein expression levels of pyroptosis-related factors NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 were detected by real-time quantitative PCR and Western-blot, respectively; the expression of Caspase-1 and IL-β protein in spleen tissue was detected by immunohistochemistry method. The results showed that compared with the control group, IL-1β in the spleen tissue of the 48, 72, and 96-hour groups was very significantly increased（P＜0.01）; IL-18 was significantly increased（P＜0.05） in the 48-hour group, and was very significantly increased（P＜0.01） in the 72, and 96-hour groups. In terms of transcription level, the NLRP3 gene was very significantly increased（P＜0.01） after PRV infection in the 48-hour group, and significantly increased（P＜0.05） in the 72, and 96-hour groups. The Caspase-1 gene was significantly increased（P＜0.05） in the 48, and 72-hour groups, and was very significantly increased（P＜0.01） in the 96-hour group. The GSDMD was very significantly increased（P＜0.01） in the 96-hour group. The IL-1β gene was very significantly increased（P＜0.01） in the 72, and 96-hour groups. The IL-18 gene was significantly increased（P＜0.05） in the 48, and 72-hour groups, and was very significantly increased（P＜0.01） in the 96-hour group. Compared with the control group, the expression of NLRP3, Caspase-1 and IL-18 proteins in the spleen cells of mice in the 48, 72, and 96-hour groups showed an upward trend, while the IL-1β protein at 72, 96 h, and the GSDMD protein at 96 h, showed a clear upward trend. Immunohistochemistry method further confirmed that Caspase-1 and IL-β proteins were up-regulated in mouse spleen. The results suggested that the PRV infection in mice could promote the inflammatory response by up-regulating the expression of pyroptosis-related factors.