Rabies post-exposure prophylaxis (PEP) remains the sole approach for preventing rabies in humans after exposure. The present study was aimed to determine the efficacy of an attenuated rabies vaccine strain (SRV-9) against lethal CVS-11 infection in CNS of mice. When CVS-11 was inoculated into mice through intramuscular (IM) route, the virus particles were detected in the CNS 3 days post inoculation and, the survival rates of mice immunized with one dose of SRV-9 at 3, 4, 5 or 6 days post exposure (PE) were 40%, 40%, 30% and 10% respectively. However, when CVS-11 was inoculated through intracerebral (IC) route, the survival rates of mice immunized with SRV9 at 0, 1 and 2 days post exposure (PE) were 30%, 10% and 0% respectively. No mice survived neither in Human Diploid Cell Vaccine ([HDCV) nor in HDCV combined with Human Rabies Immunoglobulin (HRIG) treated groups. Neutralizing antibody titers in SRV-9 immunized mice were higher than those in HDCV-treated mice by approximately 1 IU/ml. This study indicated that the highly attenuated live SRV-9 can protect mice after pathogenic CVS-11 in the CNS and might have the potential as a PEP agent for the future study.