Studies in our laboratories suggest that Sclerocarya birrea stem-bark ethanolic extract (SBE) has hypoglycemic properties. Accordingly, we investigated the effects of SBE on major complications of diabetes mellitus; blood glucose, renal function and mean arterial blood pressure (MAP) in non-diabetic and STZ-induced diabetic rats. Oral glucose tolerance test responses to various SBE doses (60, 120 and 240 mg kg(-1)) were studied in fasted rats following glucose load (0.86 g kg(-1), p.o.). Rats treated with deionized water (3 ml kg(-1) p.o.), or standard hypoglycemic drugs (insulin, 100 microg kg(-1), s.c.; metformin, 500 mg kg(-1), p.o. or glibenclamide, 500 microg kg(-1), p.o) acted as untreated and treated positive controls, respectively. Blood was collected in non-diabetic rats after 45 min of SBE, metformin or glibenclamide for plasma insulin determination. Acute SBE effects on renal function and MAP were studied in anesthetized rats challenged with hypotonic saline after 3.5h equilibration for 4h of 1h control, 1.5h treatment and 1.5h recovery periods. SBE was added to the infusate during the treatment period. Chronic effects were monitored for 5 weeks in animals daily treated with SBE (120 mg kg(-1) p.o.) while hepatic glycogen concentration was measured at the end of the experimental period. SBE exhibited dose-dependent reduction in blood glucose concentration. SBE and metformin did not affect plasma insulin secretion in non-diabetic rats, while glibenclamide increased plasma insulin concentration. The hypoglycemic effect of SBE treatment was associated with increased hepatic glycogen synthesis. Acute SBE administration did not significantly alter kidney function, but chronic SBE treatment for decreased plasma urea and creatinine concentrations of STZ-diabetic rats with concomitant increase in GFR by comparison with control rats at the corresponding period (0.7+/-0.2 vs. 1.4+/-0.3 ml min(-1)). SBE treatment reduced blood pressure in all groups of animals. The observations suggest that SBE has reno- and cardio-protective effects in diabetes mellitus. The current results indicate the basis for SBE use as complementary remedy in diabetes.