Polyimide (PI) as a typical glassy polymer material was investigated by molecular simulation to reveal the relationship between polymer molecular structure and its gas separation properties. The influences of van der waals volume (Vw) on CO2 permselectivity of PI polymers (with four kinds of backbone substitute groups and a series of side substitute groups from small to large volume) and Vw was proposed as an intermediate to establish the relationship between the substitute group and permselectivity. The results show that the CO2 permeability (P) simply increases and CO2/N2 selectivity (S) decreases with the increasing Vw of side substitute groups. The linear fitline of P-Vw is much suitable to describe and predict the effect of the increasing Vw of side substitute group on improving permeability by analyzing the experimental and calculated CO2 permeability. The increasing Vw of backbone substitute group can slow down the increasing of CO2 permeability, but result in the decreasing first and then recovering to the original level. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41082.