Various methods have been demonstrated in literature for blood cell sorting and separation as one essential step of blood sample pretreatment in both the macro and micro scale. In this chapter, the latest development of the cell/particle separation using microfluidic devices is first reviewed. Furthermore, two specific microfluidic chips developed in our group targeting blood cell separation are discussed in detail as case studies. In these two examples, pillar-type and weir-type filtration structures were designed and fabricated by microelectromechanical system (MEMS) technologies, aimed to remove Red Blood Cells (RBCs) from White Blood Cells (WBCs) based on their size differences. In these two microfluidic chips, the effects of relevant parameters (e.g., cell concentration variations and the dimensions of separation channels) on cell separation efficiency were investigated. Under the optimal condition, more than 95% RBC can be removed from the initial whole blood, while 27.4% WBC can be obtained.