The invention relates to a preparation method of silicosis mouse models. The preparation method of the silicosis mouse models is characterized in that after experiment preparation, isoflurane in an anesthesia machine is adopted to anesthetize mice in a model group, 3 seconds after rapid-shallow breaths of the mice become deep and slow, each mouse is taken out and placed at the center of a palm, the tip of a thumb presses against the underjaw of each mouse, a micropipette is adopted to instill a SiO2 micro-sized particle suspension through the nose of each mouse, the SiO2 micro-sized particle suspension is instilled into the nose wings to be absorbed, closed-chest massage is conducted for 2-3 minutes, then the mice are placed into cages, and after an experiment is finished, the mice are sent back to a normal-temperature animal feed room; only normal saline of the same volume is used for conducting nasal inhalation on mice in a contrast group; weight indexes of the mice are obtained before and after the experiment, the mice are killed at the first week, the second week, the fourth week, the eighth week and the sixteenth week respectively, lung tissue is taken to be pathologically andbiochemically compared and identified, and a model preparation effect is evaluated. According to the preparation method of the silicosis mouse models, a model production technology is stable and efficient; the method can be repeated many times and is noninvasive, environmentally friendly and humanistic, and labor and time are saved.