There is a close relationship between energy homeostasis and reproductive functions. But, the molecules responsible for this interaction remain to be explored. Nesfatin-1, an hypothalamic neuropeptide, is suggested to be another candidate for the metabolic regulation of reproductive functions besides leptin, which has been shown to exert its effects on hypothalamic-pituitary-gonadal axis by means of kisspeptin/GPR54 system. Nesfatin-1 has an anorexigenic effect1, and its circulating level is positively correlated with body mass index (BMI)2. This study was carried out to investigate whether there is an interaction between nesfatin-1 and kisspeptin/GPR54 system in terms of pubertal maturation. For this aim, the prepubertal Sprague-Dawley female rats were weaned on day 21. They were intracerebroventricularly cannulated and injected with nesfatin-1 or peptide 234, a kisspeptin antagonist, in the dose of 25 and 50 pmol, daily. Cannulation was surgically performed under general anesthesia with ketamine 60 mg/kg plus xylazine (rompun) 5 mg/kg. Puberty onset was monitored by examination of vaginal opening (VO). Body weight was daily determined, and vaginal opening was daily monitored starting from day 26. The animals were decapitated from day 60 when diestrus, which was determined by vaginal smears, was observed. Nesfatin-1 advanced VO compared to sham rats (36 versus 38 days, respectively). In the rats given nesfatin-1 and peptide 234 together, puberty onset was similar to sham rats. Pubertal weight was found to be lower (P<0.05) in nesfatin-1 injected rats compared to sham rats (73.5±2.17 and 86.9±3.55 g, respectively). Body weight was lower (P<0.003) in the nesfatin-1-injected rats compared to sham rats at the end of the experiment. Body weight was similar in the rats given nesfatin-1 and peptide 234 together. In conclusion, the nesfatin-1 seems to affect pubertal maturation by means of kisspeptin/GPR54 system in the female rats. Since obesity is suggested to advance puberty onset, nesfatin-1 may be responsible for obesity-dependent pubertal maturation.