Earlier studies revealed a general amelioration of diabetes-induced alterations in the rat following chronic oral vanadyl treatment. Recently, some streptozotocin-diabetic animals treated similarly were observed to remain euglycemic after withdrawal from vanadyl. In the present study, the diabetic profile of these animals (STZ-T) was investigated. After 3 weeks of treatment with vanadyl followed by 13 weeks of withdrawal, plasma concentrations of glucose, insulin, lipids, and thyroid hormones in the STZ-T animals were returned to control levels. Myocardial dysfunction and increased glycerol output from adipose tissue in untreated-diabetic (STZ) rats were also found to be normalized in the STZ-T group. Furthermore, there was no evidence of cataracts in these animals compared with age-matched STZ rats. These findings indicate that short-term oral treatment of diabetic rats with vanadyl induces beneficial changes that persist following withdrawal of the treatment. The results of these studies may suggest a possible new treatment protocol that could be incorporated into the management of diabetes.