Abstract: 【Objective】To explore the mechanism of signal transducer and activator of transcription 1 （STAT1） in the process of rabies virus （RABV） infection, which could provide theoretical basis for subsequent research on STAT1 function.【Method】After murine-derived astrocytes （C8-D1A） infected with RABV, the expression changes of virus genes,host cell STAT1 and cytokines were detected by real-time fluorescence quantitative PCR and western blotting at 12, 24and 48 h post infection. Different siRNA sequences were designed and synthesized according to the STAT1 gene target sequence, and the liposome was instantaneously transfected into C8-D1A cells. The STAT1-siRNA sequences with the higher interference efficiency were screened for further experiments. The selected STAT1-siRNA sequences were transfected into C8-D1A cells, and then the cells were inoculated with 0.1 MOI RABV at 24 h post infection, the effects of interference with STAT1 gene expression on RABV replication and cytokine expression were detected at transcription level and protein level respectively. 【Result】RABV infection on C8-D1A cells could cause large increase in the expression of STAT1 protein. Both the attenuated strain rRC-HL and the standard virulent strain CVS-11 infection could cause upregulation of cytokines genes including IFN-α, IFN-β, TNF-α and IL-6 in C8-D1A cells. Through the verification of the interference effect of STAT1-siRNA, it was found that after 24 h of action at the highest concentration of 200 nmol/L, the interference efficiency of STAT1-1616 was 81%, and the interference efficiency of STAT1-2271 was 82%, with extremely significant level of interference effect（P＜0.01）. After 48 h of action, the interference efficiency of STAT1-1616 was 83%, and the interference efficiency of STAT1-2271 was 75%, with significant level of interference effect（P＜0.05）.Therefore, these 2 pairs of STAT1-siRNA were selected for subsequent experiments. After interfering with the expression of STAT1 gene, both attenuated strain rRC-HL and the standard virulent strain CVS-11 showed an up-regulation trend in the expression of N and P genes. The virus N and P proteins showed an up-regulation trend at 24 and 36 h post infection,indicating that interfering with STAT1 gene expression was beneficial for up-regulating of virus protein synthesis and promoting RABV replication. However, interfering with STAT1 gene expression had no significant effect on the production of IFN-α, IFN-β, TNF-α and IL-6 cytokines induced by RABV infection （P＞0.05）.【Conclusion】The synthesized 2 pairs of STAT1-siRNA sequences（STAT1-1616 and STAT1-2271） have significant interference effects on the STAT1 gene in C8-D1A cells. Interference with STAT1 gene expression is beneficial for up-regulating virus protein synthesis and promoting RABV replication.