Abstract: Objective To investigate the effect of SEG-shRNA complex on rabies virus (RV) infected mice. Methods Forty BALB/c mice intramuscularly injected with RV PB3 street strain were randomly divided into control group, SEG group, shRNA group and SEG-shRNA group, 10 mice in each group. The control, SEG, shRNA and SEG-shRNA group were injected with saline, SEG, shRNA and SEG-shRNA respectively in tail vein after challenge for 3 days. The expression of RV mRNA and RV N protein in brain tissue were detected by qRT-PCR and Western blotting. The level of IFN- in serum was measured. Results The onset time and death time of mice in SEG-shRNA group were (170.54±11.21) h and (389.28±43.22) h respectively, which were significantly delayed compared with those in control, SEG and shRNA group (all P<0.05). The relative expression of RV mRNA and RV N protein in SEG-shRNA group were 1.002±0.321 and 0.999±0.232, which were significantly lower than those in control, SEG and shRNA group (all P<0.05). There was no significant difference in serum IFN- level in all groups (P>0.05). Conclusion SEG-shRNA complex has a certain therapeutic effect on RV infected mice and inhibits RV.