The major findings of the present study can be summarized as follows: (1) T2DM db/db mice exhibited much worse BBB permeability in acute phase after focal ischemic stroke compared to their lean db/+ counterparts; (2) delayed rFGF21 administration given 6 h after stroke onset largely mitigated the ischemia-induced BBB permeability in db/db mice; (3) the BBB-protective effect of rFGF21 was at least partially contributed by FGFR1-mediated promotion of PPARγ activity in cerebral microvascular endothelium (Figure 6). Here, FGFR1 is linked to ischemia.