The diffusion process of acids plays important roles in chemically amplified resists. Polymer matrices form diffusion paths and the structure significantly influences the behavior of acid diffusion. We have simulated the diffusions of molecules in polymer matrices by molecular dynamics in order to analyze the diffusion mechanism in chemically amplified resist systems. To represent the bulk-state conditions of the polymer film, the molecular structures were prepared under the three-dimensional periodic boundary conditions utilizing the molecular simulation software, Insight II and Discover from Molecular Simulations, Inc. This amorphous cell contained three chains of methacrylate polymers such as poly(methylmethacrylate), PMMA, poly(tert-butylmethacrylate), PtBuMA, poly(isobornylmethacrylate), PIBMA and poly(adamantylmethacrylate), PAdMA and one diffusion molecule, methanesulfonic acid, MSA. The free volumes in the system were also estimated as the volumes enclosed by the isopotential surfaces around the polymer. Molecular diffusion in the energy-minimized cell was simulated for 50 picoseconds by the molecular dynamics to determine the diffusion coefficient in the resist systems. The temperature dependence of the diffusion coefficient was studied. The flexible polymers such as PMMA and PtBuMA showed a lower activation-energy value than the rigid polymers such as PIBMA and PAdMA. It was also shown that the molecules did not always rapidly diffuse with larger free volumes, but the diffusions also depended upon the interaction with the polymer.