The present study was carried out to investigate the antihyperglycemic effect of Oxytenanthera abyssinica leaf extract and fractions. Diabetes was induced in rats by administering a single dose of 150 mg/kg of alloxan monohydrate. Single doses of 100 and 200 mg/kg of methanol extract (Met-E), n-hexane fraction (nHex-F), ethyl-acetate fraction (EA-F) and methanol fraction (Met-F) were orally administered to diabetic rats. Met-E and Met-F were selected and administered at 400 mg/kg. The plasma glucose level was checked at 0, 1, 2, 4, 8, 12, and 24 h after treatment in acute effect study. Then once daily administration dose effect of 400 mg/kg of Met-E and Met-F was evaluated in chronic study for 28 days. The dose of 200 mg/kg of Met-E and Met-F significantly (p<0.05) decreased the plasma glucose level at 12th hour after treatment while their marked decrease effect at 400 mg/kg was observed at 4th hour after treatment. The repeated administration of Met-E showed a significant (p<0.05) decrease effect in plasma glucose level at the end of 1st, 3rd and 4th weeks while Met-F showed a significant (p<0.05) decrease effect at the end of 2nd, 3rd and 4th weeks. Treatment with Met-E and Met-F reduced pancreatic tissue deterioration compared to diabetic control. The present results showed that methanol extract and fraction of Oxytenanthera abyssinica exerted antihyperglycemic effect both in acute and chronic administration, which might be due to an amelioration of alloxan-induced pancreatic islet’s tissue damages. Keywords: Alloxan, Oxytenanthera abyssinica, Antihyperglycemic effect, Pancreas, Methanol extract, Methanol fraction.