Phyllanthus sellowianus Müller Arg. (Euphorbiaceae) is a plant used in folk medicine as a hypoglycemic and diuretic agent. The present study describes the hypoglycemic effect of fractions obtained from the stem barks of P. sellowianus using a bioassay-guided fractionation protocol and streptozotocin-induced hyperglycemic mice. The aqueous extract was partitioned between dichloromethane and butanol to yield the dichloromethane (D), butanol (B) and the remaining aqueous (A) fractions. Fractions B and A, administered at the dose of 200 mg/kg p.o., caused a significant reduction in blood glucose concentration at 6 and 9 h, while the same dose of fraction D was ineffective. The reduction in blood glucose levels obtained with the B and A fractions was similar to that observed with glibenclamide (10 mg/kg) which was used as a reference for the hypoglycemic activity. Phytochemical analysis of fractions B and A revealed the presence of flavonoid compounds, of which rutin and isoquercitrin were the major constituents, respectively. The possible involvement of these flavonoids in the hypoglycemic effect of the active fractions is discussed.