Herein, we found T2DM mice hippocampus developed lower expressions of PINK1, Parkin, Atg5 and LC3II/I, downregulated phosphorylation of ULK1, elevated p62 expression, swollen mitochondria with irregular cristae morphology, accompanied by a cascade of events such as mitochondrial dysfunction, neuronal damage and cognitive impairment, which were reversed by UA treatment. This evidence concerns the gene ATG5 and type 2 diabetes mellitus.