Cucurbita ficifolia is commonly used as an antihyperglycaemic agent in Asia. However, the mechanism of its action is unknown. Chemically synthesized D-chiro-inositol (D-CI), a component of an insulin mediator, has been demonstrated to have antihyperglycaemic effects in rats. In this study, we found that C. ficifolia contained fairly high levels of D-CI, thus, C. ficifolia may be a natural source of D-CI for reducing blood glucose concentrations in diabetics. We evaluated C. ficifolia fruit extract, containing D-CI, for its antihyperglycaemic effect in streptozotocin-induced diabetic rats. Oral administration of C. ficifolia fruit extract containing 10 or 20 mg D-CI kg(-1) body weight for 30 days resulted in significantly lowered levels of blood glucose, and increased levels of hepatic glycogen, total haemoglobin and plasma insulin. An oral glucose tolerance test was performed in fasted diabetic and normal rats, in which there was a significant improvement in blood glucose tolerance in the diabetic rats treated with C. ficifolia fruit extract. The effects were compared with 20 mg kg(-1) body weight chemically synthesized D-CI. Findings from this study demonstrated that C. ficifolia fruit extract was an effective source of D-CI for its hypoglycaemic effects in rats, and therefore may be useful in the treatment of diabetes.