The influences of aggregate and interfacial transition zone (ITZ) on the carbonation resistance of cement-based materials cannot be ignored. Based on Fick's second law, a CO2 diffusion model considering the influences of aggregate and ITZ is proposed in this work. Subsequently, the computing methods of corresponding parameters in this model are presented. A CO2 reaction model based on the law of conservation of mass is also proposed. The reliability of theoretical modelling was further verified by comparisons with experimental data from the literature. Finally, this model was used to study the concentration distribution of CO2 in C30 and C50 concrete with and without load effects. The results showed that the carbonation prediction method considering the influences of aggregate and ITZ was capable of handling the diffusivity of CO2 in cement-based materials. This theoretical model can predict the carbonation depth values with reasonable accuracy. Therefore, this model can be used as a practical tool considering the existence of aggregate and ITZ as a significant factor to evaluate the durability of concrete. Thus, it can help to design and predict the service life of reinforced-concrete structures.