Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism. The experimental design was a split plot, with cow as the whole plot, treatment as the whole-plot factor, and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: the control (no infusion) or infusion (1,500 g/d of glucose infused into the abomasum from the day of calving). Cows were sampled at 12 d prepartum and at 4, 15, and 29 DIM. To study portal-drained visceral uptake of arterial glucose, [U-(13)C]glucose was continuously infused into the jugular vein on sampling days. Postpartum, voluntary dry matter intake and milk yield increased at a lower rate with the infusion compared with the control. The net portal flux of glucose increased with the infusion compared with the control, and 67 +/- 5% of the infused glucose was recovered as increased portal flux of glucose. The net hepatic flux of glucose was lower with the infusion compared with the control; however, the net hepatic flux of glucose per kilogram of dry matter intake was not affected by treatment. The arterial concentrations of glucose and insulin decreased and concentrations of nonesterified fatty acids increased from prepartum to 4 DIM with the control, but these effects were not observed with the infusion. The arterial concentration of beta-hydroxybutyrate decreased more from prepartum to 4 DIM with the infusion, compared with the control. Uptake of arterial [U-(13)C]glucose in the portal-drained viscera was affected neither by the infusion nor by the DIM and averaged 2.5 +/- 0.2%. The whole-body glucose supply changed to be less dependent on the recycling of lactate (Cori cycle) with the infusion. It was concluded that small intestinal glucose absorption is an efficient source of glucose to the peripheral tissues of dairy cows in very early lactation. At least 67% of the available glucose was recovered in the portal vein without affecting hepatic gluconeogenesis. Infused cows produced less milk and had a lower feed intake, indicating that an improved glucogenic status in very early lactation impaired metabolic adaptations to lactation.