In this study, we found that inhibition of immunoproteasome LMP2 enhanced the levels of ischemia-induced components of the BBB, upregulating occludin, claudin-1 and ZO-1 protein expression, improving BBB permeability, and promoting the upregulation of Wnt-3a and β-catenin proteins in rats after MCAO/R. The gene discussed is CLDN1; the disease is ischemia.