The hypoglycemic activity of the flavonoids rich fraction of 70% alcohol extract of the Egyptian Morus alba root bark (MRBF-3) was evaluated after its oral administration to streptozotocin-induced diabetic rats. Diabetes was induced by injection of 60 mg kg(-1) i.p. The administration of MRBF-3 to streptozotocin (STZ)-diabetic rats for 10 days in a dose of 200 and 400 mg kg(-1)day(-1) was not significant. However, administration of MRBF-3 for 10 days (600 mg kg(-1)day(-1)) significantly reduced the amount of the glucose from control level (379+/-9 mg/dl) to a lower level (155+/-8 mg/dl) and significantly increased the insulin level from control (10.8+/-0.3 microU/ml) to a high level (15.6+/-0.3 microU/ml). The measurement of produced lipid peroxides (expressed as the amount of thiobarbituric acid (TBA) reactive substance, nmol TBARS/ml serum) indicated antiperoxidative activity of MRBF-3. The oral administration of MRBF-3 to STZ-diabetic rats significantly decreased the lipid peroxides from 6.3+/-0.8 to 5.1+/-0.7 nmol TBARS/ml serum. The phytochemical investigation of MRBF-3 resulted in the isolation of four hydrophobic flavonoids with one or two isoprenoid groups (log P=5-9): morusin, cyclomorusin, neocyclomorusin, and kuwanon E, a 2-arylbenzofuran, moracin M, and two triterpenes, betulinic acid and methyl ursolate. The data obtained from this study revealed that MRBF-3 may protect pancreatic beta cells from degeneration and diminish lipid peroxidation. However, this is the first biological screening of the Egyptian Morus alba root bark; further future merit studies including clinical study will be necessary in order to confirm the results obtained from this study.