The aqueous extract of the leaves of Leonotis leonurus (L.) R. Br. at the doses of 125, 250 and 500 mg/kg body weight was investigated for toxicity in male rats following administration on daily basis for 21 days. The extract did not significantly (p > .05) alter the levels of haemoglobin, packed cell volume, mean corpuscular volume, red cell distribution width, basophils, total protein, phosphorus, calcium and chloride ions of the animals. Whereas the levels of lymphocytes, eosinophils, monocytes, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, atherogenic index, albumin as well as alkaline phosphatase and gamma glutamyl transferase activity were decreased by the extract, those of neutrophil, magnesium, total and conjugated bilirubin, alanine and aspartate aminotransferase as well as liver and kidney body weight ratios increased. There was decrease in the mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and cholesterol only at the 500 mg/kg body weight of the extract, whereas the large unstained cells, sodium ions, white blood cells and uric acid increased only at 250 and 500 mg/kg body weight of the extract, respectively. The urea, creatinine and potassium increased only at 125 mg/kg body weight of the extract while the globulin content was elevated only at 500 mg/kg body weight of the extract. The doses did not produce any definite pattern of effect on the red blood cells and platelets. These alterations by the aqueous extract of L. leonurus leaves on the haematological together with the liver and kidney functional indices suggests parameter and dose-selective effects of the extract and will have consequential effects on the normal functioning of the blood system, kidney and liver of the animals. The extract is also unlikely to predispose the animals to cardiovascular risk when repeatedly consumed on daily basis at the doses investigated for 21 days. Therefore, the aqueous extract of L. leonurus leaves may not be 'safe' as oral remedy in male rats.