In order to develop high energy density Li rechargeable batteries, nano-sized materials have attracted attention as the active materials. Mesoporous materials consist of the micrometre-sized particles, and they have high surface area due to their mesopore and thin wall thickness of framework. Here, we synthesize a highly ordered mesoporous RuO2 to investigate the effect that the mesoscopic structure has on the capacity and their corresponding reaction mechanism of Li rechargeable battery. The synthesized mesoporous RuO2 shows an initial discharge capacity of 1366 mAh g−1 on mesoporous RuO2, which is higher than that of commercial RuO2. Our findings via In situ X-ray analysis techniques combined with electrochemical analysis demonstrate that the additional capacity of mesoporous RuO2 is resulted from the enhanced interfacial reaction between Ru metal and Li2O formed by conversion reaction of RuO2. Nano-size effects of mesoporous structure such as high surface area, easy electron transport, and small domain would enable to improve the interfacial reaction of highly ordered mesoporous RuO2. The understanding of this relationship between structural engineering and electrochemical properties provides the insight into development of high energy density anode materials in next generation Li rechargeable battery.