Aim: To investigate effect of the nociceptin/orphanin FQ (OFQ) on hypothalamus gonadotropin-releasing hormone (GnRH) release in ovariectomized (OVX)rats. Methods: GnRH radioimmunoassay (RIA) was used to study the effect of OFQ on GnRH release in hypothalamus slices in vitro. Push-pull perfusion and intracerebroventicular (icv) injection were used to examine the effect of OFQ on GnRH release in the hypothalamus medial preoptic area (POA) in vivo. Ovariectomies were performed on female Sprague-Dawley rats, and their plasma luteinizing hormone (LH) levels were measured after icv injection of OFQ with or without [Nphe1]NC(1-13)NH2, a competitive antagonist of opioid receptor-like1 receptor (ORL1 receptor). Reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate the expression of the ORL1 receptor in rat pituitary. Results:GnRH release from hypothalamus slices was inhibited 90 min after the administration of 2 mmol/L and 20 mmol/L OFQ (P＜0.05). Accordingly, GnRH release from hypothalamus POA was also significantly reduced by the injection of 0.2 mmol/L and 2 mmol/L OFQ. Plasma LH levels were also decreased significantly 2 h after icy injection of 20 nmol OFQ in OVX rats (P＜0.05) and this effect could be abolished by pretreatment with 20 nmol [Nphe1]NC(1-13)NH2, that is, NC13. More interestingly, plasma LH levels in OVX rats increased markedly 2 h after icv injection of 100 nmol and 200 nmol NC13. RT-PCR analysis further revealed that the ORL1 receptor was not expressed in the pituitary of OVX rats. Conclusion: Central administration of nociceptin/orphanin FQ might inhibit the release of hypothalamic GnRH and decrease the plasma LH levels through ORL1 receptors in OVX rats.