Abstract: A permanent catheterization of the jugular vein and the hepatic portal vein in rats is described. The rat was anesthetized with pentobarbital (25 mg/kg, ip) during surgery. The catheterization of the jugular vein was performed in a similar way as Upton's method (1975). The catheterization of the portal vein was established at the author's lab. The peritoneal cavity was opened via a midline incision. The pyloric vein was exposed. A silicone tubing (0.28 mm I.D., 0.61 mm O.D.) filled with heparinized saline was inserted into the pyloric vein towards the portal vein and secured by sutures. The abdominal opening was closed, allowing for the catheter to be brought under the skin and exposed at the back of the animal. The tubing was plugged. Rats were housed individually which posed no problems upon their health and activity. If daily flushings were performed, the tubings might remain functional for several weeks. Injections and blood samplings could be conveniently achieved every minute. After sampling (approximate 0.25 ml) the same volume of blood obtained from other healthy rats by heart puncture was transfused. The technique described herein was designed for pharmacokinetic and first pass metabolic studies, as well as for numerous other applications, as much for liver as for intestinal biochemistry and physiology. This technique involves a simple, rapid and less traumatic surgical procedure, requiring neither elaborate preparation nor equipment more specialized than medical-grade tubing. Dosings and samplings can be performed repeatedly in unanesthetized, unrestrained rats instantancously. The animals can be crossed over after a wash-out period.Study of the pharmacokinetics of promethazine hydrochloride was performed in catheterized rats (N=9, iv 5 mg/kg). The results are as follows. T_1/2(α): 0.11±0.026(h), T_1/2(β): 1.8±0.79(h), Vc(L/kg): 2.1±0.55, CL(L/kg×h): 3.76±2.75. The first pass effects on the bioavailability of promethazine hydrochloride was also studied. Each rat received the doses (5 mg/kg) via oral, iv and intraportal vein. The rats were crossed over after a 72h wash-out period. The results are as follows, AUC(ng×h)/ml: iv, 1633.9±370.0, portal vein: 318.5±174.1. oral: 173.0±219.7, respectively.