Objective: To establish an animal model of non-transthoracic cardiopulmonary bypass (CPB) in rats. Methods: Ten adult male Sprague-Dawlay rats, weighing 350-500 g, were used in this study. CPB was established in these animals through cannulating the left carotid and right jugular vein for arterial perfusion and venous ret. The components of perfusion circuit, especially the miniature oxygenator and cannula, were specially designed and improved. The mean arterial pressure was measured with a blood pressure meter through cannulating the left femoral artery. The hemodynamic and blood gas parameters were also monitored. Results: The rat model of non-transthoracic CPB was established successfully. The hemodynamical parameters were changed within an acceptable region during CPB. The miniature oxygenator was sufficient to meet the standard of satisfactory CPB.Conclusions: The rat model of non-transthoracic CPB established through the carotid and jugular cannulation is feasible, easily operated, safe, reliable, and economic. It is an ideal model for the pathophysiological research of CPB.