Technical Abstract: Our previous studies in neonatal piglets showed that compared to enteral nutrition, total parenteral nutrition (TPN) leads to mucosal atrophy and reduced portal blood flow. Moreover, infusion of the trophic gut hormone, GLP-2, increases portal blood flow and prevents mucosal atrophy in TPN fed piglets. Among GI tissues, the GLP-2 trophic effect and the most abundant GLP-2 receptor expression are localized in the small intestine. Thus, we hypothesize that GLP-2 dose dependently increases SMA blood flow in TPN fed piglets. In study 1, 2-wk-old pigs (N=3) were implanted with duodenal, jugular and carotid catheters and an ultrasonic flow probe on the SMA. After recovery and 4 d of enteral feeding, pigs were fasted overnight then given 8h enteral feeding followed by 12h of TPN. In study 2, 3-d-old pigs (N=3) were implanted with jugular and carotid catheters and a SMA flow probe; flow probes were placed on the celiac artery (CA) in two separate pigs. After surgery, pigs were placed on TPN and continued for 7 d. In all pigs, SMA or CA flow was measured during a 2-h saline baseline infusion followed by 2-h GLP-2 infusions at doses ranging from physiologic (62.5 pmol/kg/hr) to pharmacologic (125, 250, 500, 1000 pmol/kg/hr). Mean SMA flow during enteral feeding was 34% higher (p< 0.05) than during TPN. GLP-2 dose dependently increased SMA flow based on both 2-h area under the curve (AUC) and 1-h infusion time point. For AUC, GLP-2 stimulated SMA flow was 22%, 26%, 56%, 66%, and 103% above the saline baseline (P <0.05), respectively for each increasing GLP-2 dose. GLP-2 did not significantly increase CA flow at any dose. We conclude GLP-2 dose dependently increases SMA flow, but not CA arterial flow in TPN fed piglets consistent with the relative expression of GLP-2 receptor in gastrointestinal tissues. Pharmacologic doses of GLP-2 stimulate SMA flow in excess of that observed with enteral nutrition.