Available evidence suggests that Sclerocarya birrea stem-bark extract (SBE) which possesses hypoglycaemic activity may be useful in the treatment and management of diabetes mellitus. Since diabetes is associated with cardiovascular and kidney complications, we investigated the influence of SBE on blood glucose, blood pressure and renal function in some experimental animal paradigms. For OGTT tests, separate groups (n=6 in each group) of non-diabetic and streptozotocin-(STZ)-treated diabetic rats fasted for 18 hours were given glucose (0.86 g.kg−1 body weight, p.o.) followed by SBE at various doses (60, 120, 240 mg.kg−1). Animals treated with deionised water (3 ml.kg−1) or metformin, (500 mg.kg−1) served as untreated and positive controls, respectively. Blood glucose was monitored at 15 minute intervals for the first hour, and hourly thereafter for 3 hours. Acute renal effects were assessed by urine flow, Na+ and K+ excretion rates in anaesthetized rats challenged with hypotonic saline infusion at 30-min intervals for 4 h of 1 h control, 1½ h treatment and 1½ h recovery periods following equilibration period (3½ h). SBE was added to the infusate during the treatment period. Renal effects were also monitored in individually-caged rats administered daily with SBE for 5 weeks. The hypotensive effect of SBE was examined in anaesthetized and conscious normotensive rats, while myocardial contractile performance was evaluated on guinea-pig isolated atrial muscle strips. SBE dose-dependently decreased blood glucose within the first 30 minutes in non-diabetic and STZ-diabetic rats. Similar effects were observed with metformin. Na+ and K+ excretion rates were not altered by acute or chronic treatment with SBE. The extract caused significant reduction in blood pressure in anaesthetized and conscious rats. SBE also produced concentration-dependent, significant (P<0.01) negative inotropic and chronotropic effects on guinea-pig isolated, electrically-driven left-, and spontaneously-beating right-, atrial muscle preparations, respectively. The current observations suggest that SBE has a cardioprotective role in management of diabetes mellitus.