Background; -Rabies is viral zoonotic disease progressive neurological infection which causes rnencephalitis in all warm-blooded animals. Dogs are the greatest reservoir host and transmit therndisease to other animals and man. It is 100% fatal after the on-set of clinical manifestation of therndisease. Plants are widely used conventionally for the treatment of rabies and contribute to therndevelopment of modern drug and treatment of this disease. rnObjective: -The objectives of this study was to assess the acute toxicity and anti-rabies activityrneffect of C. kilimandschari, K. lanceolate and S. abyssinica, traditionally used for the treatment ofrnhuman rabies. rnMethods: - An experimental study was conducted between February, 2020 and June, 2021. In vivornacute toxicity and anti-rabies activity test was done in 78 Swiss albino mice. Extract was preparedrnfrom the powdered study plant using 70 % hydro-ethanol and concentrated by using rotaryrnevaporator. Blood samples were collected for the assessment of biochemical parameters. Brainrnsamples were collected for confirmatory test of rabies virus. Data was analyzed using SPSS versionrn26 for windows software, Statistical analysis was undertaken by one-way analysis of variancern(ANOVA). rnResults; -In this experiment, 20,15and 30gm crude extract / yield/ obtained from 100gm powderedrn70%hydro ethanol extracted of C. kilimandschari, K. lanceolate and S. Abyssinia respectively.rnThe crude extract of S. Abyssinica did exhibit sign of toxicity at dose 550mg/kg treatment groupsrnof mice, The LD50 of Abyssinica was 560mg/kg.C. Kilimandschari and K. lanceolate did notrnexhibited any sign of toxicity at all doses levels. The level of serum enzyme ALPand CHO ofrnmice treated with C. Kilimandschari were highly reduced. However, ALT, AST, BILD, BILT,rnUrea and K were increased in treated mice with K. lanceolate compared to negative control. Allrnplant crude extract did show significantly(p