This research delves into the impact of coarse aggregate particle size on the mechanical properties of concrete. Nano-indentation and scanning electron microscope (SEM) techniques were applied to characterize the micro-properties and thickness the Interfacial Transition Zone (ITZ). The effect of coarse aggregate size on concrete's compressive strength (σc) and elastic modulus (E) and the relationship between the micro properties of the ITZ and the macro properties of concrete were discussed. In addition, Griffith's microcrack theory was adopted to explain related mechanisms. The relationship between the microscopic properties of the ITZ and the macroscopic properties of concrete was discussed. The results show that, in concrete with a low water cement-ratio w/c (0.3), thickness of ITZ increased with the coarse aggregate size and concrete properties decreased. While, in concrete with a higher w/c (0.4), there exists an optimum coarse aggregate size for the lowest thickness of ITZ and highest strength. Taking the ITZ as the initial crack in concrete failure, concrete properties can be linked to ITZ thickness from Griffith's microcrack theory.