The internal defect is an important factor that could influence the energy and safety properties of energetic materials. RDX samples of two qualities were characterized and simulated to reveal the influence of different defects on sensitivity. The internal defects were characterized with optical microscopy, Raman spectroscopy and microfocus X-ray computed tomography technology. The results show that high-density RDX has fewer defects and a more uniform distribution. Based on the characterization results, defect models with different defect rates and distribution were established. The simulation results show that the models with fewer internal defects lead to shorter N-NO2 maximum bond lengths and greater cohesive energy density (CED). The maximum bond length and CED can be used as the criterion for the relative sensitivity of RDX, and therefore defect models doped with different solvents are established. The results show that the models doped with propylene carbonate and acetone lead to higher sensitivity. This may help to select the solvent to prepare low-sensitivity RDX. The results reported in this paper are aiming at the development of a more convenient and low-cost method for studying the influence of internal defects on the sensitivity of energetic materials.