Introduction: 5-Hydroxytryptamine (5HT) and kisspeptin are satiety factors, and ghrelin and adiponectin are orexigenic peptides. In this study, the mediating role of 5HT in the effects of GPR54 receptor blocking on ghrelin and adiponectin secretion was investigated. Methods: Male Wistar rats weighing 220-250 g received saline, kisspeptin 10 (1 or 3 nmol), 5HT (2, 5 or 10 µg), kisspeptin plus 5HT, or peptide 234 (P234) plus 5HT via the third cerebral ventricle. Serum ghrelin and adiponectin concentrations were determined using the enzyme-linked immunosorbent assay method. Results: Kisspeptin or 5HT treatment significantly reduced serum concentrations of ghrelin and adiponectin in comparison with saline. The injection of 2 nmol of P234 + 5HT significantly reduced serum ghrelin concentration compared to the 5HT alone, kisspeptin alone, and kisspeptin + 5HT groups. Injections of either 1 or 2 nmol of P234 along with 5HT significantly declined the mean serum adiponectin level compared to rats received the kisspeptin plus 5HT. Conclusion: Kisspeptin/GPR54 signaling pathway may be a putative target in serotonergic neurons to control ghrelin and adiponectin secretion.