We investigated the variability in amino acid sequences between mitochondrial cytochrome c oxidase subunit II (COII) domains, as well as that of gene sequences encoding the corresponding domains. According to the secondary structure, COII consisted of five domains of N- and C-terminal regions posited in the intermembrane space, two transmembrane helices (TM1 and TM2) in the lipid bilayer, and a matrix-embedded loop (ML) that intervened between the two helices. Our analysis, using dictyopteran insects as model species, revealed that amino acid and nucleotide substitution rates were heterogeneous between the COII domains. The amino acid substitution rates were higher in the TM1 ($0.380{pm}0.123$) and ML domains ($0.416{pm}0.184$),whereas they were relatively lower in the N-terminal ($0.204{pm}0.123$) and TM2 domains ($0.184{pm}0.088$). As expected by the variability in the amino acid substitution rates, the average nucleotide substitution rates were also relatively higher in the TM1 ($0.312{pm}0.081$) and ML domains ($0.302{pm}0.093$), whereas the lowest substitution rate was observed in the N domain ($0.191{pm}0.073$). These results indicate that the heterogeneous substitution rates between COII domains, as well as genes encoding the domains,might be closely related to the inner membrane environment where each region of the amino acid sequence is laid.