Apheresis is a procedure used to fractionate whole blood into its individual components. Following fractionation, the desired component is isolated and the remaining blood in many cases is returned to the donor. Leukapheresis is one type of apheresis where leukocytes (white blood cells) are selectively removed. This procedure is commonly used for blood transfusions to remove donor leukocytes from being transferred to the recipient. Apheresis also has several therapeutic applications. In this manuscript we discuss the design, fabrication and testing of a continuous flow diffusive filter, fabricated using simple soft lithographic techniques for depletion of leukocytes. This device employs micro sieves that exploit the size and shape difference between the different cell types to obtain depletion of leukocytes from whole blood. Currently, conventional apheresis methods like centrifugation or fiber mesh filtration are commonly used. A theoretical model was developed to determine the optimal shape of the diffuser to ensure that the volumetric flow through individual sieve elements is equal. This device was designed to serve as a passive device that does not require any external manipulation. Results show that for the given device design, isolation of ∼50% of the inlet erythrocytes (red blood cells), along with depletion of >97% of the inlet leukocytes is possible at a flow rate of 5 μl min-1. Simple modifications to the geometry and dimensions of the sieves can be made to obtain isolation of plasma. © The Royal Society of Chemistry 2006.