Malarial multiple-drugs resistant parasite is the main problem in treatment of malaria and need efforts in finding and development of new effective antimalarial drugs. Combination of antimalaria with synergistic activity is one of recommendation ofWorld Health Organization by using artemisinin based combination therapy. This study is aimed to evaluate the antimalarial activity of eurycomanone alone and in combination with artesunate on Plasmodium berghei strain ANKA infected mice. In vivo antimalarial activity were done by using modified 4-days suppressive test. One hundred adult male albino mice were randomly divided into ten groups with10animalseach.Experimental mice consist of malarial infected mice(group I) that only received aqua pro injection. Malarial infected mice in groups II to VIreceived3.75; 7.50; 15; 30 mg/kg BW/day of eurycomanone and 4 mg/kg BW/day of artesunate, respectively.Group VII to X are malarial infected mice which were given combination of eurycomanone-artesunate according to the doses above and all treated drugs used intramuscularly for four days. The result of this study have been shown that eurycomanone possessed ED50 value 16.29 mg/kgBW. The percentage of growth inhibition of P. berghei by combination of eurycomanone-artesunate with doses 30 mg/kgBW-artesunate 4mg/kgBW is 99.34%. Based on statistic analysis this combination can be used as potential antimalarial drug.