Leptin and its receptor are widely distributed in several tissues, mainly in white adipose tissue. The serum leptin is highly correlated with body mass index in rodents and humans, being documented that leptin levels reduces in the fasting state and increase during refeeding, similarly to insulin release by pancreatic islets. Insulin appears to increase leptin mRNA and protein expression and its release by adipocytes. Some studies have suggested that insulin acts through the activation of the transcription factors: sterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein-α (C/EBP-α) and specificity protein 1 (Sp1). Insulin stimulates the release of preformed and newly synthesized leptin by adipocytes through its signaling cascade. Its effects are blocked by inhibitors of the insulin signaling pathway, as well as by inhibitors of protein synthesis and agents that increase the intracellular cAMP. The literature data suggest that chronic hyperinsulinemia increases serum leptin levels in humans and rodents. In this review, we summarized the most updated knowledge on the effects of insulin on serum leptin levels, presenting the cell mechanisms that control leptin synthesis and release by the white adipose tissue.