Continuous emergence of multi-drug-resistant malaria parasites and their rapid spread across thernglobe warrant urgent search for new anti-malaria chemotherapeutics. Traditional medicinalrnplants have been the main sources for screening active phytochemicals against malaria.rnAccordingly, this study was aimed at evaluating the anti-malarial activity of Osyris quadripartitarnDecn.which is used for malaria treatment by local people around Fiche, north-central Ethiopia.rnUsing aqueous, chloroform and methanol crude leaf extracts of the plant have been prepared andrntested for toxicity and anti-malarial efficacy in Plasmodium berghei-infectedSwiss albino mice.rnMethanol solvent gave the highest yield of the plant extract. Acute toxicity study resultsrnindicated that the plant extract did not show any sign of toxicity up to 2000mg/kg. To assess therneffect of the plants on the parasite, a 4-day suppressive standard test was performed. Data werernanalyzed using paired t-test and ANOVA. Both aqueous and methanol extract of O.quadripartitarnsignificantly (P