Cortistatin (CST), a novel neuropeptide, shows high structural homology and functional resemblance with somatostatin. CST binds with high affinity to all somatostatin receptors, and contrary to somatostatin, is also able to bind with MrgX2 and GH secretagogue receptor of ghrelin (GHS-R1) receptors. The aim of the present investigation was to evaluate in vivo the effect of peripheral administration of cortistatin on pituitary hormone release in comparison with somatostatin (SS) treatment. Adult male rats used in the experiment, were given peripheral injection of cortistatin, somatostatin or vehicle. Blood was withdrawn 60 and 120 minutes thereafter. We found short lasting significant decrease of GH concentration as a result of administration of CST and SS when compared with saline injected controls. Prolactin levels were increased 60 min after cortistatin but not to somatostatin injection. There was no effect of CST on both LH and FSH concentration; however, SS administration influenced gonadotropin secretion. We conclude that cortistatin play a regulatory role in pituitary secretion. Moreover, some differences have been found when compared cortistatin to somatostatin. Thus, when analyzing the mechanism of cortistatin activity it is worth to consider the effect of binding with receptors of somatostatin, specific receptor for CST (MrgX2) and GHS-R.