We previously reported effects of diosgenin on cognitive function in normal mice and Alzheimer’s disease model mice and healthy humans. The low oral bioavailability of diosgenin has been well recognized. However, our previous study showed that diosgenin dissolved in olive oil was efficiently distributed in the brain and exerted a memory-enhancing effect in mice after oral administration. This study investigated potencies of olive oil, fish oil and medium-chain triglyceride to transfer diosgenin in the brain. Diosgenin detected in the cerebral cortex after oral administration was very high in case of dissolved in olive oil. Brain penetration of diosgenin dissolved in fish oil was lower than that in olive oil. Medium-chain triglyceride showed very low potential of brain penetration of diosgenin after p.o. administration. We found in this study potencies of transporting diosgenin to the brain were different by fats as solvents.