Maternal plasma leptin is elevated during pregnancy in several species, but it is unclear to what extent this elevation reflects changes in adiposity or energy balance. Therefore, Karakul ewes (n = 8) were fed to minimize changes in maternal energy status over the pregnancy-lactation cycle. They were studied 20-40 d before breeding and during mid pregnancy (d 50-60 post coitus [PC]), late pregnancy (d 125-135 PC) and early lactation (d 15-22 post partum). Consistent with the maintenance of near energy equilibrium in nongravid maternal tissues, maternal body weight was increased only during late pregnancy when the weight of the conceptus became significant and plasma concentrations of insulin, NEFA and glucose did not vary with physiological state. In contrast, maternal plasma leptin concentration rose from 5.3 to 9.5 ng/mL between prebreeding and mid pregnancy and then declined progressively through late pregnancy and early lactation. Leptin gene expression increased 2.3 fold in maternal white adipose tissue (WAT) from prebreeding to mid pregnancy and declined to prebreeding levels during early lactation. To determine whether tissue response to insulin was involved in this effect, insulin tolerance tests were performed. The maternal plasma glucose response declined from prebreeding to early lactation, but was not correlated with either plasma leptin concentration or WAT leptin mRNA abundance. In conclusion, pregnancy causes an increase in the synthesis of leptin in sheep. This stimulation does not require increases in adiposity or energy balance and is unrelated to the ability of insulin to promote glucose utilization.