The purpose of this research is to elucidate the regulatory functions of sesamin and episesamin from sesame seeds against retention in vivo and metabolism of essential fatty acids, especially arachidonate (AA,n-6), eicosapentaenoate (EPA,n-3) and docosahexaenoate (DHA,n-3). At first simultaneous determination method of sesamin and episesamin was established using HPLC. Then, metabolism of sesamin and episesamin in vivo was measured. They were easily metabolized in vivo and diappeared up to 24 hr. This result suggested that their metabolites function for regulation of metabolism of essential fatty acids. After administration of AA, EPA or DHA, respectively, accumulation of these fatty acids in the tissues was observed, but sesamin and episesamin reduced their concentrations in various tissues and retained the homeostasis of fatty acid concentrations. So, sesamin and episesamin including their metabolites will act as regulatory substances for metabolism of essential fatty acids of both n-6 and n-3 series.