Viscosity of blood substitutes is among the important determinants to restore microcirculation. Sodium alginate (SA) is always mentioned as "viscosity modifier" in creating blood substitutes. In the present study, the whole blood was diluted using SA solutions to final hematocrits of 10%, 20%, and 35%, respectively. The whole blood viscosity (WBV) at different shear rates, plasma viscosity (PV), and rheological behavior of red blood cells (RBCs) was studied in vitro. The results show that SA may induce RBCs aggregation in a dose-dependent manner. Furthermore, the effect of SA on RBCs aggregation maybe involve the regulation of microcirculation.