Aggregate and interfacial transition zone (ITZ) have significant influence on the carbonation resistance of cement-based materials. Based on Fick's second law, a CO2 diffusion model considering the influence of aggregates and ITZ is proposed in this paper, the diffusion coefficient of interfacial transition zone is introduced for the first time and the calculation method of corresponding parameters in this model is given. At the same time, a CO2 reaction model is established based on the law of mass conservation, and the CO2 concentration distribution in C30 and C50 concrete under load is studied by using this model. The results show that the diffusion coefficient and depth of carbonation of CO2 in cement-based materials can be calculated more accurately by considering aggregate and ITZ effects. Finally, the reliability of the theoretical model is further verified by comparing with the experimental data in literature. Therefore, the model takes aggregate and ITZ as important factors to evaluate the durability of concrete, which provides foundation for the design and life prediction of reinforced concrete structures.