Mulberry (Morus indica L.) leaves, the sole food of the silk worm, were evaluated for antidiabetic effects in streptozotocin (STZ)-diabetic rats. Treatment with dried mulberry leaf powder at 25% of the diet for a period of 8 weeks was found to be remarkably beneficial to STZ-diabetic rats as evidenced by controlled hyperglycemia and glycosuria. In addition, mulberry leaves countered (reversed) the alterations in gluconeogenic substrates in STZ-diabetic rats as indicated by significant reduction in serum pyruvic and lactic acid levels, a significant increase in proteins and a significant decrease in free amino acid, urea, and creatinine levels in blood, and a decreased urinary excretion of urea and creatinine. Anomalies in the activities of hepatic gluconeogenic enzymes associated with impaired glucose homeostasis in STZ-diabetic rats were ameliorated by feeding the mulberry leaf-supplemented diet, indicating that control over hyperglycemia and associated complications in the diabetic state by mulberry leaves is by way of regulation of gluconeogenesis. With respect to all the parameters, mulberry leaves were more effective than the oral hypoglycemic drug glibenclamide.