The present study aims mainly to determine the best way to stop rabies infection in naturally exposed victims through the application of antiviral treatment in a comparison with the efficacy of emergency immunization using rabies antiserum and vaccine. All tested concentrations of ribavirin and Acyclovir did not inhibit the cell growth rate and did not affect the cell morphology indicating the drug safety. In vitro studies revealed that 1-200 μg of ribavirin or acyclovir were able to inhibit the CPE of 100 TCID50 of rabies virus in infected BHK cell culture confirming their antiviral effect. Administration of ribavirin and acyclovir as emergency treatment of rabies infection simulating in mice, revealed that the best time for ribavirin treatment was restricted between 0 time (time of infection) and 2 days post infection showing 100% protection followed by the treatment on the 3rd day post infection (90% protection) then the 4th day (70% protection). Delayed treatment leads to less protection (40% decreased gradually to 10% by the 5th to 7th day post infection. More delayed treatment resulted in 0% protection. Administration of acyclovir on 0 times; 1; 2 and 3 days post experimental infection of mice with rabies virus was able to overcome virus infection recording 100% protection followed by 80% protection with treatment application on the 4th day. Mice receiving acyclovir after that were unable to withstand the clinical signs of rabies starting from 60 to 0%. Administration of rabies hyper immune serum to experimentally infected mice revealed 100%; 90%; 80% and 70% protection when such administration was carried out on 0, 1, 2, 3 and 4 days post infection respectively. Delayed administration of rabies hyper immune serum resulted in decrease of the protection % from 50% by the day 5 to 0% by the day 7 post infection. These results investigate that ribavirin, acyclovir and rabies antiserum could be administrated to overcome rabies infection on the main time post exposure.