The invention belongs to the field of pharmaceutical engineering and biotechnology and particularly relates to a model for establishing an internal barrier crystal structure by software, as well as a preparation method and an application thereof. The molecular dynamics simulation is carried out by computer software such as NAMD, DS, MS, GROMACS, AMBER, VMD, CHARMM or the like, and parameters such as a diffusion coefficient and the like are calculated by analyzing the indexes such as mean square displacement and the like, so that the permeability of drugs to be screened or researched on blood-brain barrier, skin barrier, gastrointestinal barrier, nose barrier, oral mucosa barrier, neural presynaptic and postsynaptic membranes and cell membranes can be detected. A model platform established by an external computer can be used for quickly and effectively screening the effective drugs permeable to the blood-brain barrier, the skin barrier, the gastrointestinal barrier, the nose barrier, the oral mucosa barrier, the neural presynaptic and postsynaptic membranes and the cell membranes, so that the model has an important application value in the aspect of new drug screening. Meanwhile, the model can be used for simulating the diffusion and release actions of the drugs in nanoliposomes or similar lipidosomes, so that the model also has a wide application prospect in the field of pharmaceutical preparations.