A simple new method is described for chronic cannulation of the portal vein in rats. A Silastic catheter (0.64 mm OD) with an internal metallic leader is directly inserted in the junction of the two small ileal veins. The catheter is advanced into the mesenteric vein to the portal vein. Then the leader is removed and the catheter tunneled out the back of the neck. This method allows for the measurement of portal vein pressure, direct injection of substances in the portal vein, or blood samples for at least 1 wk in intact unrestrained rats. Validation included the presence of elevated portal vein pressure in portal hypertensive rats compared with normal rats and the absence of clot development in the portal vein. This method should help provide a better understanding of hepatic physiology and pharmacology in normal and disease states.