The objective of this study was to investigate the effects of Orthosiphon stamineus Benth. aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. The chemical screening of the extract showed phenolic compound and flavonoid content were 13.24+/-0.33 mg/g and 1.73+/-0.14 microg/g, respectively. In oral glucose tolerance test, the extract (0.2-1.0 g/kg) significantly decreased plasma glucose concentration in a dose-dependent manner in both normal and diabetic rats. The extract at 1.0 g/kg was most effective in decreasing plasma glucose concentrations and the response was closed to the result of glibenclamide (5 mg/kg). After repeated daily oral administrations of the extract (0.5 g/kg) for 14 days, the extract significantly reduced plasma glucose concentration in diabetic rats at days 7 and 14. By the end of the study, plasma triglyceride concentration was lower in the extract-treated diabetic rats than untreated ones. Furthermore, plasma HDL-cholesterol concentration was significantly increased in diabetic rats treated with the extract. In perfused rat pancreas, the extract did not increase insulin secretion in the presence of 5.5 mM glucose, but 100 microg/ml extract potentiated glucose-induced insulin secretion. Our findings suggested that Orthosiphon stamineus aqueous extract is effective for alleviating hyperglycemia and improving lipid profile in diabetic rats.