The safety of the ethanol stem bark extract of Dichaetanthera africana (DABE) was evaluated. A single oral dose of 1000 and 2000 mg/kg bw was administered to the rats in the acute toxicity study and the animals observed for 7 days. The crude extract was given by daily oral administration of 250-1000 mg/kg bw for 28 and 90 days respectively in the sub-chronic toxicity test. Body weight, rectal temperature, food and water consumptions were recorded weekly. Hematological and biochemical parameters and relative organ weights (liver, kidney, heart, and spleen) were determined at the end of the 28 and 90-day administration. Histopathological examination of the liver and kidney of rats was done. No adverse effects or mortality were observed throughout the period of the acute toxicity experiment (LD 50 ˃ 2000 mg/kg). DABE did not produce any mortality and there were no significant differences between groups in daily oral administration for 28 days. For 90 days, DABE caused behavior adverse effects at the dose of 1000 mg/ kg bw. DABE resulted in significant changes in biochemical parameters at the dose of 500 and 1000 mg/kg bw. Liver histopathology revealed morphological alteration at these doses. The results suggested that DABE is relatively nontoxic in daily oral administration for 28 days. However, it becomes toxic for 90 consecutive days at the doses of 500 and 1000 mg/kg bw.