Cardiopulmonary bypass (CPB) is indispensable for cardiac surgery. Since the ethical and technical difficulties associated with clinical research limit the acquisition of new knowledge, it is desirable to have a miniature extracorporeal circulation (ECC) system for small animals. We aimed to establish a miniature ECC system and apply the system to the rat for investigating systemic inflammatory response changes during and after CPB. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride) and a roller pump. Priming volume of this system is only 7 ml. Rats were divided into the SHAM (received surgical preparation only without CPB) group and the CPB group. ECC pump flow was initiated and maintained at 70 ml/kg/min. We measured the serum cytokine levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and biochemical markers (lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) before, 30, and 60 min after the initiation of CPB, in addition, 30, 60, and 120 min after the CPB weaning. During CPB, blood pressure and hemoglobin were maintained around 80 mmHg and 10g/dl, the serum cytokine levels and biochemical markers were significantly elevated in the CPB group compared with the SHAM group. These data suggest that CPB promotes organ damage and a systemic inflammatory response. This rat ECC model is considered to be equivalent to the already established human CPB and useful for studying the mechanism of pathophysiological changes during and after CPB.