Background: The burdens of substance use and disorders are becoming a worldwide problem.rnOne of the psychostimulant plants widely consumed in Ethiopia and other East African countriesrnis Catha edulis Forsk (khat). Its effects on hematologic and hemodynamic indices, serumrnelectrolytes, and neurobehavioral effects and their relationship have not been fully investigatedrnin animal model.rnObjective: The present study was aimed to investigate hematologic, hemodynamic, serumrnelectrolyte and neurobehavioral effects of khat in animal models.rn Materials and Methods: the khat was collected from the natural habitats and the edible partsrnwere separated and freeze-dried to be crushed using mortar and pestle. The crushed materialsrnwere measured and extracted using diethyl ether and chloroform (3:1 v/v ratio). A total of 98rnadult (6-7 weeks) Swiss albino mice of both sexes with an average weight of 27.61 gm and 42 (78rnweeks)rnmalernSwissrnalbinornratsrnwithrnan averagernweightrnofrn221.89 gmrnwerernused.rnMicernreceivedrnrn2%rntweenrn80rninrndistilledrnwaterrn(T80W-rnv/v)rnandrnkhatrnextractrnsubchronicallyrn(kesc)rn(100rnmg/kg,rnrn200rnmg/kg,rn300rnmg/kg)rnforrntwelvernweeksrnandrnsubacutelyrn(kesa)rn(300rnmg/kg)rnforrneightrndays.rnMicernrnreceivedrnrnkhat extract at alternative days during conditioned place preference study for 20rndays. Rats also received similar doses of the khat extract for twelve weeks. Ascorbic acid (AArn200 mg/kg) and khat juice (khJ 2.5 ml/kg) was also administered to rats subchronically. Khatrnextract was also administered subacutely (kesa) (300 mg/kg) for eight days to rats. rnHematological indices and hemodynamic effects of khat extract and juice were determined usingrnSysmex KX-21 and ultrasonic Doppler flow meter, respectively. The serum electrolytes andrnprefrontal cortex malondialdehyde levels were measured using Cobas 6000 andrnSpectrophotometer, respectively. Elevated plus-maze, conditioned place preference, Morrisrnwater maze and novel object recognition tests were used to evaluate the neurobehavioral effectsrnof khat. Data were analyzed using SPSS version 21.0 and graphs were plotted using MicrosoftrnExcel. rnResults: The total body weight of mice and rats was not affected by khat (p>0.05). However, thernsize of brain at higher dose was reduced (p