Pig to human cardiovascular xenotransplantation can be an option for the treatment of the patient with terminal heart function. Transgenic modifications of pig organs have proven some degree of amelioration of acute phase rejections. In this study, we developed an ex-vivo cardiovascular perfusion system to assess the interaction between the pig endothelium and human blood. Farm pig heart was arrested with 4 ��� University of Wisconsin solution (UWS) and harvested immediately after arrest. Explanted heart was perfused with human whole blood through both coronary arteries using our perfusion system consisting of membrane oxygenator, roller-pump and reservoir for 3 h. Time-dependent changes of isolated pig myocardium were evaluated by histopathologic examination, immunohistochemistry and differentially increased gene expressions. Also serum, and plasma at each time points from 0 to 3 h were analyzed. Pig hearts showed typical widespread histologic features of hyperacute rejection in myocardium and immunohistochemical analysis of myocardium showed depositions of human C5b-9, IgM, IgG. Following exposure to human blood, pig hearts showed increased gene expressions related to immune rejections. Also serum analysis showed time-dependent linear increase in GOT, GTP, LDH, Troponin I, and CK-MB. These data reported here may provide reference values for investigators to further study the xenogeneic immune reaction, tolerability, pharmacokinetics, and exploring new molecules that to be clarified in cardiovascular xenotransplantation.