Malaria is the one among the greatest important tropical diseases, the highest cause of rnhospitalization and the major fatal parasitic killer disease of the world. Due to the emergence of rnresistance to the currently available drugs, the need for new targets and relevant antimalarial rnagents remains urgent. Like many other developing countries, people in Ethiopia use the rntherapeutic benefits of traditional medicine for malaria treatment. In the present study the rnantimalarial activity of the leaf extract of Osyris quadripartita Salzm. ex Decne and its main rnconstituent has been assessed. The leaves of O. quadripartita were collected, dried under shed rnand extracted with 80% methanol. The hydroalcoholic extract was further subjected to silica gel rncolumn chromatography and eluted successively with chloroform, chloroform-methanol (3:1), rnchloroform-methanol (1:1), and methanol mobile phase to obtain four fractions designated as F-1, rnF-2, F-3 and F-4, respectively. Analytical TLC of F-2 showed the presence of a pure flavonoid rncharacterized as (-)-catechin by MS, rnmeasurement of optical activity. rn1rnH-NMR, rn13rnC-NMR and DEPT spectral data as well as by rnFourteen days after oral administration, the 80% MeOH leaf extract or the isolated compound to rnmice at a fixed dose of 2,000 mg/kg produced no signs of toxicity or motality. Evaluation of the rnantiplasmodial activity of the hydroalcoholic extract and (-)-catechin by Petersâ€™ 4-day suppressive rntest revealed that both the test substances inhibit in vivo growth of Plasmodium berghei in mice. rnAt doses of 100, 200 and 400 mg/kg of body weight, the hydroalcoholic extract and the isolated rncompound suppressed growth by 54.69, 62.04 and 70.61% and 42.55, 54.47 and 64.26%, respectively. The present study confirmed that the leaf extract of O. quadripartita possesses rngenuine in vivo antimalarial effect against P. berghei in mice. Therefore, the hopeful activity rnprofile of the extract and isolated compound parallel with their relative margin of safety provision rnthe traditional claim of the plant for the management of malaria.