To determine if increased glucose demand affects feed intake or hepatic metabolism, 12 lactating Holstein cows were treated with phlorizin or control in a crossover experiment. Phlorizin injected subcutaneously at 4 g/d caused 474 g/d of glucose excretion in urine. While treatment caused a decrease in lactose synthesis and milk production, feed intake and 3.5% fat-corrected milk production were not altered by treatment. The lost glucose was likely accounted for by increased gluconeogenic flux. Hepatic pyruvate carboxylase mRNA concentration increased with phlorizin treatment, suggesting that retention of glucose precursors may be involved in regulation of gluconeogenesis.