Bulbine natalensis stem extract (25, 50 and 100 mg/kg body weight for 14 days) did not significantly alter the red blood cell count, haemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width in male Wistar rats. In contrast, the white blood cell count increased by the end of the experimental period. While the levels of neutrophils, lymphocytes and eosinophils decreased after the administration of single dose of the extract (day 1), those of the platelets and monocytes increased. The extract also reduced the levels of basophils and large unstained cells after the seven daily doses. All the doses increased the serum concentrations of cholesterol and triacylglycerols. Whereas the serum concentration of low-density lipoprotein was unaffected throughout the experimental period, the decrease in high-density lipoprotein cholesterol was accompanied by increase in the atherogenic index. The results showed that aqueous extract of B. natalensis stem exhibited localized systemic toxicity mainly on the white blood cell count and related indices. The alterations in the serum lipid profile may predispose the animals to atherosclerosis especially when consumed repeatedly for two weeks.