We examined whether intraportal delivery of NPY affects glucose metabolism in 42-h-fasted conscious dogs using arteriovenous difference methodology. The experimental period was divided into three subperiods (P1, P2 and P3). During all subperiods, the dogs received infusions of somatostatin, intraportal insulin (3-fold basal), intraportal glucagon (basal), and peripheral intravenous glucose to increase the hepatic glucose load 2-fold basal. Following P1, in the NPY group (n=7), NPY was infused intraportally at 0.2 and 5.1 pmol·kg^-1·min^-1| during P2 and P3, respectively. The Control group (n=7) received intraportal saline infusion without NPY. There were no significant changes in hepatic blood flow in NPY vs Control. The lower infusion rate of NPY (P2) did not enhance net hepatic glucose uptake (NHGU). During P3, the increment in NHGU (compared with P1) was 4±1and 10±2 µmol·kg^-1·min^-1 in Control and NPY, respectively (P<0.05). The increment in net hepatic fractional glucose extraction during P3 was 0.015±0.005 and 0.039±0.008 in Control and NPY, respectively (P<0.05). Net hepatic carbon retention was enhanced in NPY vs Control (22±2 vs 14±2 µmol·kg^-1·min^-1, P<0.05). There were no significant differences between groups in the total glucose infusion rate. Thus, intraportal NPY stimulates hepatic glucose uptake without significantly altering whole body glucose disposal in dogs.