Vanadium, an important trace element in nutrition, actively affects the metabolic activities on all tissues. This work reports the effects of vanadate on leptin production from adipocytes isolated from normal Sprague-Dawley rats, streptozotocin-induced diabetic rats, Zucker lean, and Zucker fa/fa rats. We found that vanadate stimulates leptin production similar to insulin. The maximum leptin production stimulated by vanadate was slightly higher than that by insulin. Treatment with vanadate or insulin also increased the cellular leptin mRNA levels in a ratio similar to the increase in the protein secretion, suggesting that the regulation is at the transcription level. For adipocytes isolated from both streptozotocin-induced diabetic rats and Zucker fa/fa rats, vanadate was a more potent stimulant than insulin on leptin production. This suggests that vanadate may stimulate leptin production by mechanisms that are independent of insulin receptors.