Updated FTP location. Diabetes is at an increased risk for development of dementia and effective treatments for diabetes-induced dementia are required with urgency. Yokukansan, a Kampo medicine, is used clinically to treat several neurological conditions including dementia. In this study, we aimed to show the effects of yokukansan on learning and memory functions in diabetes-induced dementia and to clarify the molecular mechanisms inducing the effects in the hippocampus of yokukansan- and non-treated diabetic model mice. Morris water maze test showed that yokukansan admin-istration significantly improved learning and memory functions of diabetic model mice. In the proteomic analysis, significant changes in expression of 10 (4 up- and 6 down-regulated) proteins and 8 (3 up- and 5 down-regulated) phosphoproteins were observed in the hippocampus of yokukansan-treated diabetic model mice. These identified proteins and phosphoproteins could be functionally classified as neuronal development, cellular cytoskeleton, energy metabolism, oxi-doreductase, protein deubiquitination, proton transport, and chaperone. Additionally, western blotting validated the changes in CAPZB, tubulin beta-5 chain, and LDHB. Taken together, these results showed that yokukansan improved learning and memory functions in mice with diabe-tes-induced dementia, underlying the changed expression of proteins and phosphoproteins in the hippocampus. We propose that yokukansan could be effective for care of diabetes-induced de-mentia.