A systematic equilibriummolecular dynamics study was performed to investigate the diffusion rates of gas molecules as a function of the pressure in metal-organic frameworks (MOFs) with different structures. Methane was chosen as the probe molecule. The self-diffusion coefficients in eight typical MOFs were calculated at roomtemperature. Combined self-diffusion coefficients with the contour plots of the center of mass (COM) probability densities of methane, the relationship between the diffusion rates of gas molecules and the structure of the pores in the MOFs is discussed. Results show that methane tends to adsorb in pockets in MOFs with pocket and channel pores (P-C materials) at low pressure. With an increase in pressure, the gas molecules move to the channel and the self-diffusion coefficient increases. However, the diffusion coefficient of methane changes a little in the low and middle pressure range in the IRMOFs (isoreticularMOFs) with only one kind of pore.With a further increase in pressure, the self-diffusion coefficient of methane decreases in all the studied MOFs. Therefore, the difference in diffusion rates of methane in different MOFs may be mainly attributed to the pore structures of the materials. In addition, diffusion rates of the gas molecules in the P-C materials could be controlled in a wide range by varying the pressure, providing useful information for the application of MOFs in gas storage and separation.