Based on the microfluidic chip processing technology and using the microscopy-micromodel experimental system, the seepage experiment was performed by fabricating the quasi-two dimensional microfluidic chip model to imitate the internal skeleton and pore structure of porous media. The permeability of chip model was calculated by measuring and modifying the pressure drop of both end of the chip model. Computational fluid dynamics (CFD) method was adopted to make the numerical simulation of the seepage process compared with the results of experiment. Under the same condition, compared with the chip model with the square arrangement micro-pillar, the chip model with staggered micro-pillar showed that the tortuosity increased with an amplitude of 5.1%—7.9% microscopically, the flow resistance and pressure drop increased and the permeability decreased with an amplitude of 4.5%—7.4% macroscopically. The permeability of chip models was not only related to the internal pore structure and porosity, but also related to particle diameter and particle arrangement. When the porosity of model was 0.327—0.900, the permeability of the chip model obtained by the numerical simulation method was closed to the experimental results with the error of 9.78%—28.43%. Kozeny-Carman (KC) equation could not predict the experiment results correctly and the maximum error was 73.97%. A modified parallel plate duct flow equation was proposed to predict the permeability of quasi-two dimensional microfluidic chip model. The curve of predicted permeability was consistent well with the numerical and experimental data.nt well with the numerical and experimental data.