The adhesion of red blood cells (RBC) has been studied extensively in frame of cell-to-cell interaction induced by dextran macromolecules, whereas the data are lacking for native plasma solution. We apply optical tweezers to investigate the induced adhesion of RBC in plasma and in dextran solution. Two hypotheses, cross-bridges and depletion layer, are typically used to describe the mechanism of cell interaction; however, both mechanisms need to be confirmed experimentally. These interactions in fact are very much dependent on the size and concentration of dextran and proteins in plasma. The results show that in different dextran solutions, the interaction of adhering RBC agrees well with the quantitative predictions obtained based on the depletion-induced cells adhesion model, whereas the migrating cross-bridges model is more appropriate for plasma. Despite the different mechanisms of RBC interaction in a mixture of dextran with the size ranges and volume fraction proportional to plasma proteins, the dependence of RBC adhering tends to be close to the cross-bridges model. The induced aggregation of RBC in the dextran solutions and in native plasma are observed by direct visualization utilizing scanning electron microscopy.