In conclusion, our present work provided the evidence that DPP-4 inhibition with linagliptin following transient cerebral ischemia ameliorates blood-brain barrier breakdown and oxidative stress, and thereby counteracts the impairment of cognitive function and brain atrophy due to the reduction of hippocampal and cortical neuronal cell in type 2 diabetic mice. This evidence concerns the gene DPP4 and brain ischemia.