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Abstract: Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset was monitored by means of scoring the moment of vaginal opening (VO). Median VO age was higher (35days versus 27days) in FR animals but leptin levels at VO were significantly decreased (1.44±0.17ng/ml versus 2.79±0.31ng/ml). Centrally (icv) and peripherally (sc) infused leptin (1μg/day) advanced VO age compared to FR controls (30days versus 35days and 31days versus 41days, respectively). Congruently, centrally (icv) administered leptin-antiserum (0.6μg/day) delayed puberty onset. In normally fed rats median VO age was only marginally advanced (26days versus 27days) but only if leptin was applied centrally. The effects of FR on puberty onset are counteracted or even normalized by the infusion of leptin, whereas immunoneutralization of central leptin postpones puberty onset. We therefore conclude that central leptin is crucial for initiating puberty in female rats. [Copyright &y& Elsevier]