Abstract: Hymenocardia acida leaf extract is used folklorically as remedy for fever, pain and respiratory diseases. It has also been shown to possess antisickling, antioxidant, antiulcer, anti-arthritic and mutagenic properties, among others. This study was undertaken to ascertain the acute and sub chronic toxicity profile of H. acida ethanol leaf extract administered orally in rats. Acute toxicity test was carried out using modified Lorke's method. Four groups of seven rats each were used for sub chronic toxicity evaluation. The first group served as control, while groups two, three and four received 25, 50 and 100 mg kg-1 extract respectively for twenty-nine days. In the acute toxicity test, the extract did not cause any signs of toxicity or produce mortality in rats. Results also showed that sub chronic administration of the extract did not significantly (p>0.05) affect food consumption, body weight and haematological parameters at the doses used. Water intake was observed to increase significantly (p<0.01) in the groups administered 25 and 50 mg kg-1 extract during the first and fourth weeks of administration. Relative spleen weights were significantly (p<0.05) lowered in groups given 50 and 100 mg kg-1 extract while relative brain weight reduced significantly (p<0.05) in the group administered 100 mg kg-1 extract. Serum triglyceride levels were also significantly (p<0.01) elevated in 50 and 100 mg kg-1 extract-treated groups, without significant alterations of other biochemical parameters. Microscopically, mild cortical-tubular cellular oedema in kidneys of extract-treated groups was observed. This study shows that although H. acida leaf extract is safe acutely, its long-term use of may be associated with mild renal toxicity.