Adenosine modulates the intestinal functions of secretion, motility, and immunity, yet little is known about regulation of nutrient absorption. Therefore, we measured carrier-mediated uptake of tracer (2 µM) ¹⁴C-D-glucose by everted sleeves of mouse intestine after lumenal exposure to adenosine and a disodium salt of adenosine 5'-monophosphate (AMP). Rates of glucose uptake by intact tissues increased almost 2-fold after a 7 min exposure to 5 mM adenosine (a physiologic dose). The response was slightly more pronounced for AMP, and could be induced by forskolin. The response to adenosine was blocked by theophylline and the A₂ receptor antagonist 3,7-dimethyl-1-proparglyxanthine, but not by the A₁ receptor antagonist 8- phenyltheophylline. Glucose uptake by control and AMP stimulated tissues was inhibited by phloridzin, implying SGLT1 is the responsive transporter, but the involvement of GLUT2 cannot be excluded. Of clinical relevance, AMP accelerated systemic availability of 3-O-methylglucose glucose after oral administration to mice. Our results indicate adenosine causes a rapid increase in carrier-mediated glucose uptake that is of clinical relevance, and acts via receptors linked to a signaling pathway that involves intracellular cAMP production.