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Anogeissus leiocarpus is a plant/ herb used for the traditional treatment of various ailments, including diabetes mellitus by many rural communities in Africa. The active principles of the herb have been defined, but there is no documented report about the effects of extracts of the stem barks of this herb on body fluids. In this study, we report for the first time, the clinical presentation, haematological changes, variation in biochemical profiles and the resistance of the red cell mass of Wister rats administered ethanolic extracts of the stem barks of the herb to osmotic stress (erythrocyte osmotic fragility, EOF). The clinical signs observed following administration of the herb include anorexia, dullness, rough hair coats and huddling. There was no statistically significant difference (p>0.05) in mean red blood cell counts of all the experimental groups, compared to the control. Mean packed cell volume (PCV) was statistically significantly elevated (p<0.05) in some experimental groups, while mean corpuscular volume (MCV) was elevated in others, compared to the control. Total leucocytes (WBC) did not vary significantly (p>0.05) in all the groups, compared to the control. Differential leucocytes were essentially similar (p>0.05) in all the experimental groups investigated. Platelet counts statistically significantly decreased (p < 0.05) in all but the experimental group administered 500 mg/kg of extract, compared to the control. Mean EOF significantly decreased (p<0.05) in some groups, while mean serum glucose levels decreased significantly (p<0.01) in all the experimental groups, except the control. The implications of these findings in relation to the use of the herb are discussed. It is concluded that for the herb to be certified safe for clinical use to ameliorate diabetes, it must be administered in combination with an expicient that modulates thrombocytopaenia.