Fructose 2,6-bisphosphate concentration, 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase2) activity, and messenger RNA decreased in maternal rat liver during the last days of gestation, and the recovery started after delivery. Phospho(enol)pyruvate carboxykinase activity and messenger RNA increased in contrast to PFK-2 changes. Measurement of the glycolytic capacity in isolated hepatocytes prepared from rats 1 h after parturition showed a low glucose consumption and an impaired capacity to metabolize glucose. These results stress the relevance of the PFK-2/fructose 2,6-bisphosphate system in the control of the glycolytic flux in liver, and these changes are intended to prevent glucose consumption by maternal liver and contribute to allow gluconeogenesis to proceed at the end of gestation. The physiological basis of this adaptation may lay on the diversion of glucose from maternal to fetal metabolism.