Success of a blood transfusion lies in significant reduction of white blood cells. Differences in density, structure, geometry and size of white and red blood cells are the reasons behind different behavior these cell during separation process. High flexibility of red blood cells facilitate their passage through very narrow channels. Characteristics of the white blood cells allow their separation from blood using fibrous filter media. Thus, optimization of white blood cell filtration is of vital importance as far as separation performance is concerned. Conducted research in the field of white blood cell separation modeling is rather scarce. Optimization of white blood cell filtration depends up on modelling of fibrous media structural parameters of the fibrous media and their effect on separation process. In this work, nano-spun polyacrylonitrile-dimethylformamide fibrous filter media were produced. The effect of structural parameters such as fiber fineness, fiber orientation, pore size and surface roughness on white cell separation efficiency of the produced filters were evaluated using image-processing method. White cell separation performance and safe use of the produced filters were insured, using a set of designed experiments together with the equations governing filtration principals and the relevant internationally accepted standards. In order, Response surface methodology was used to develop a statistical model capable of predicting the most influential factors affecting white blood cell filtration. It was concluded that white blood cell separation efficiency is highly affected by the pore size, number of constituent layers and their weight per unit area. Produced filters were found to be capable of reducing the number of white blood cell by five logarithm which is two logarithm lower than the threshold stated in the CE standard. It was also established that while the produced filters like their commercial leukofilter counterparts possess higher separation ability than the stated thresholds in the standards, the produced filters were lighter than the commercial leukofilter by 94% weight wise. It was deduced that the asymmetric filter media compose of produced filters in comparison to symmetrical filter media and the commercial leukofilter membrane have superior separation ability. Model generated results pointed to conformity of separation mechanism of the produced filters with principals governing depth filtration and standard blocking. Results of the response surface methodology respectively pointed to conformity of number of residual white blood cell, red blood cell recovery percent and filtrate volume with Quadratic, reduced 2FI and reduced linear functions. It was established that fiber fineness and layers weight per unit area of the produced filters significantly affect white blood cell filtration.