This study was carried out on apparently, healthy 20 lambs (4-6 months old) were selected from private flock in Dakahalia governorate without previous history of nervous manifestations and 30 rabbits were used for experimental vaccination with live Listeria monocytogenes vaccine and were classified into three groups(10 in eachgroup). The vaccine was evaluated humerally by detection of antibodies titer and cellular activity through measuring of Nitric oxide and lysozyme in sheep and rabbit. While the protection aganist challenge and reisolation were used in rabbits Immune response of sheep vaccinated with Listeria monocytogenes vaccine showed increase in serum neutralizing antibody titers which gradually increased after 2nd dose of injection till reach maximum level at 15 days of the second dose compared with non vaccinated control sheep. This result stated that the Vaccination of rabbits and sheep with live Listeria monocytogenes (1/2a and 1/2b) vaccine induce cellular and humeral response and protect the vaccinated rabbits against challenge with Listeria monocytogenes.