Erythrocyte adhesion to the vascular endothelium is one of the key determinants of microcirculatory blood flow. Adhesion is a complex process determined by the intricate interaction among red blood cells (RBC), plasma factors, and the vascular endothelium. Rats are commonly used as disease models to investigate the pathophysiology of various hematological disease processes occurring in humans and their response to prospective treatments. The aim of our study was to characterize the adhesion of RBC in adult blood from rat and human subjects, in order to test the validity of rat models for adhesion-related disease processes. We demonstrated that adhesion of RBC from rats (rRBC), to endothelial cells (EC) in plasma-free buffer, is stronger than from human subjects (hRBC). In addition, plasma proteins induced elevation of hRBC (eightfold) but depression of rRBC (threefold) adhesion to EC. It is thus suggested to be aware of the difference in RBC/EC interaction for human and rat subjects, when studying models of blood flow.