Although treatment with antipsychotics, particularly olanzapine and clozapine, has been implicated in weight gain and higher incidence of diabetes, the mechanism of these adverse reactions remains unclear. The purposes of this study were to explore the early effects of olanzapine on serum levels of ghrelin, adiponectin and leptin, three recently identified hormones that play crucial roles in the regulation of energy balance and glucose metabolism. Thirteen patients with schizophrenia who had not received any medication in the 4 weeks prior to this study were included. The patients received olanzapine at an average dose of 14.5mg/day. Serum levels of ghrelin, adiponectin, leptin and insulin, as well as weight and fasting glucose, were investigated at the baseline and at 4 weeks. Serum ghrelin levels had decreased (p 0.03) and leptin had increased (p 0.02), while adiponectin and insulin levels had not significantly changed at Week 4 (p 0.29 and p 0.25, respectively). Weight had increased (p 0.01), while fasting glucose had not significantly changed (p 0.46). These findings suggest that ghrelin levels decrease and leptin levels increase after initiation of olanzapine therapy. Weight gain is also considered to be an early change, while change in insulin sensitivity is not an early change of treatment with olanzapine. Further large-scale and longitudinal studies are warranted to elucidate metabolic changes involving ghrelin, adiponectin, leptin and insulin and their impact on weight and glucose metabolism during treatment with olanzapine and other antipsychotics.