Abstract: Anti-malarial property and toxicity of methanolic extract of leaves of Tithonia diversifolia and Morinda lucida were investigated in mice and rats, respectively. Percentage parasitemia and chemosuppresive effect of the extract on Plasmodium berghei infected mice were used to assess anti-malarial property while toxicity was evaluated by measuring the activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and some selected tissues as well as evaluation of some hematological parameters, serum electrolytes, urea and creatinine in rats. The extract at 200 mg kg-1 b.wt. showed significant (p<0.05) chemo suppressive effect following five days administration in P. berghei established infection. There was a significant decrease (p<0.05) in the liver, kidney and serum activities of ALT following 7 and 14 days administration of the extract. Similar trends were observed in liver and serum ALP and liver AST. However, there was a significant increase (p<0.05) in kidney and serum AST activity for both periods of administration except for the significant decrease (p<0.05) in the kidney following the 14 days administration. The white blood counts showed a significant decrease (p<0.05) following administration of T. diversifolia for 7 and 14 days and M. lucida for 14 days while administration of both extract for 14 days revealed a significant increase (p<0.05) in platelet counts. Serum bicarbonate, chloride, sodium, potassium and urea decreased significantly (p<0.05) following administration of the extract for 7 and 14 days. This result therefore suggests that, methanolic extract of T. diversifolia and M. lucida possess considerable anti-malarial property but may potentiate some level of toxicity especially if administration is prolonged.