Objective To study the effect from drug diffusion coefficient of atherosclerotic plaque on drug diffusion within the arterial wall, so as to truly reflect the drug distributions. Methods Using computational fluid dynamics (CFD) method, five plaque models with different diffusion coefficients were employed to numerically investigate the distributions of drug concentration both within the arterial wall and the plaque. Results The drug concentration in the arterial wall was increased gradually with the diffusion coefficient of the plaque increased; however, the increment would become gentle. Conclusions When the diffusion coefficient in the plaque was smaller than the tissue, the plaque inhibited the drug diffusion within the arterial wall, or conversely, it would promote the diffusion. Especially when the diffusion coefficient in the plaque was much larger than the tissue, it no longer affected the drug diffusion within the arterial wall. It is necessary to consider the impact of plaque in further research, which is beneficial to the optimization design of drug-eluting stents.