This research is aimed to characterize the elastic properties of carbon nanotubes (CNTs) reinforced polyimide nanocomposites using multi-scale simulation approach. The hollow cylindrical molecular structures of CNTs were modeled as a transverse isotropic solid the equivalent elastic properties of which were determined from the molecular mechanics calculations in conjunction with the energy equivalent concept. In addition, the molecular structures of the CNTs nanocomposites were established through molecular dynamic (MD) simulation, from which the non-bonded gap as well as the non-bonded energy between the CNTs and the surrounding matrix were evaluated. It was postulated that the normalized non-bonded energy (non-bonded energy divided by surface area of the CNTs) is correlated with the degree of interfacial interaction. Subsequently, an effective interphase micromechanical model including the equivalent cylindrical solid of CNTs, matrix and effective interphase was developed, in which the dimension of the effective interphase was assumed equal to the non-bonded gap and the corresponding elastic stiffness was calculated from the normalized non-bonded energy. Results indicated that the moduli of the nanocomposites in the longitudinal direction obtained based on the effective interphase model are in good agreement with those calculated from MD simulation and moreover, they are fitted well with the conventional rule of mixture. On the other hand, in the transverse direction, the effective interphase model is superior to the conventional micromechanical model and capable of describing the dependence of Young's modulus of the nanocomposites on the CNTs radii.