Introduction: Rat models of cardiopulmonary bypass (CPB) have been used to examine the mechanisms of associated organ damage and to test intervention strategies. However, these models only partly mimic the clinical situation, because of the use of blood transfusion and arterial inflow via the tail artery. Thus a model using arterial inflow in the aorta and a miniaturized CPB circuit without need of transfusion was validated by examining intra-procedure characteristics, mortality and the effects of CPB on biomarkers of inflammation and cerebral injury during 5 days follow-up. Methods: Male Wistar rats (n=95) were anesthetized with isoflurane (2.5%) and fentanyl/midazolam during CPB. Animals were assigned to Control (n=6), Sham (n=40) or normothermic CPB (n=49) groups. Both Sham and CPB were cannulated in the aorta via the left carotid artery and in the right common jugular vein for access into the right heart. Extracorporeal circulation (ECC) was instituted for 60 min only in CPB at a flow rate of 120 mL kg(-1) min(-1) employing a CPB circuit of 15 ml primed with 6% hydroxyethyl starch 60 mg ml(-1) solution. Rats were sacrificed at either 1 h or 1, 2 or 5 days after Sham or weaning from CPB. Plasma IL-6 and s100Beta levels were measured and blood cell counts were performed. Results: Mortality in CPB animals (3 out of 49) and Sham (4 out of 40) did not differ (chi-square=0.46, dF=1, P>0.5). Compared to baseline (1.87+/-0.46*10 boolean AND 9 cells/L), Sham procedure (cannulation and anesthesia) significantly increased blood neutrophil count at the end of the period matching ECC (6.34+/-2.36*10 boolean AND 9 cells/L, P