Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation， and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice. Methods Forty?eight male C57/BL6 mice were randomly assigned to four groups： the control group， the low?dose group， the medium?dose group， and the high?dose group. The low?dose， medium?dose， and high?dose groups received 62.5 mg/mL， 125 mg/mL， and 250 mg/mL neodymium oxide， respectively， via non?exposed tracheal instillation. The control group received an equivalent volume of saline using the same administration method. After 35 days， the mice were euthanized， and brain tissues were collected. RT?PCR was used to assess the mRNA expression changes of Claudin?5 and Occludin. Western blot analysis was performed to evaluate the expression changes of Claudin?5 and Occludin tight junction proteins， as well as the expression changes of MMP?2 and MMP?9 in the brain tissues. Additionally， the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined. Changes in oxidative stress markers， including MDA， T?AOC， and NO， were measured using a kit method. Results The mRNA expression of Claudin?5 was significantly reduced in the middle?dose and high?dose groups compared to the control group （P < 0.05）. Similarly， the mRNA expression of Occludin was significantly lower in the low?dose， medium?dose， and high?dose groups compared to the control group （P < 0.05）. Additionally， the protein expression of Claudin?5， MMP?2， and Occludin was significantly decreased in the low?dose， medium?dose， and high?dose groups compared to the control group （P < 0.05）. The protein expression of MMP?9 and RhoA was also significantly lower in the medium?dose and high?dose groups compared to the control group （P < 0.05）. Furthermore， the protein expression of ROCK2 and p?cofilin in the high?dose group was significantly lower than that in the control group （P < 0.05）. The content of MDA and T?AOC was significantly lower in the medium?dose and high?dose groups compared to the control group （P < 0.05）， and the content of NO in the high?dose group was significantly lower than that in the control group （P < 0.05）. Conclusion Exposure to neodymium oxide results in increased permeability of the blood?brain barrier in mice， leading to oxidative stress， inflammatory responses， and activation of the RhoA/ROCK2 signaling pathway.