It was previously found that the expression of peroxisome proliferator-activated receptor-a (PP ARa) was markedly augmented in the liver of suckling rats, in comparison to the fetuses and most notably to adult rats and it paralleled similar changes in hepatic lipid concentration. To determine whether these changes could be related to the high lipid content of the maternal milk and/or to hormonal status, the role of changes in nutrient availability and in plasma insulin concentration on liver expression during the perinatal stage in vivo in the rat was studied. When suckling rats were weaned on day 17, instead of on day 20, the level of hepatic PPARa mRNA decreased earlier than in rats weaned later. When 10-day-old rats were force-fed with either glucose or Intralipid or a combination of both diets, it was found that, at similar low levels of plasma insulin, a high level of FFA stimulated PPARa expression, whereas, at similar high plasma FF A concentrations, an elevated insulin level attenuated the increase in PPARa expression. It is proposed that both the high lipid intake and decreased plasma insulin level are responsible for the high PP ARa expression detected in rat neonates.