We compared the physiological activities of sesame seeds rich in lignans from three varieties (Gomazou, Maruhime and Maruemon), and those from a conventional cultivar (Masekin) in rats. The sum of the values of fat-soluble lignans (sesamin and sesamolin) in seeds of Gomazou, Maruhime and Maruemon varieties was approximately double the value in Masekin. Seeds from Maruemon contained fat-soluble lignan most exclusively as sesamin while other varieties contained sesamin and sesamolin at about a 2:1 ratio. After a 16 d experiment, sesame seeds, added at 200 g/kg to the experimental diets, increased the activity and mRNA levels of fatty acid oxidation enzymes. Increases were stronger with seeds rich in lignans than with seeds from Masekin. In contrast, sesame seeds lowered the activity and mRNA levels of lipogenic enzymes. However, sesame seeds from all the varieties were comparable in affecting these parameters. Serum triacylglycerol concentrations were lower in rats fed diets containing sesame seeds rich in lignans than in those fed a diet free of sesame seeds or a diet containing seeds from the Masekin variety. Serum malondialdehyde (a marker of lipid peroxidation) was lower in rats fed diets containing sesame seeds rich in lignans than in those fed a sesame seed-free diet or Masekin diet. It is apparent that sesame seeds rich in lignans, irrespective of lignan composition, more profoundly affect hepatic fatty acid oxidation and serum triacylglycerol levels and possibly attenuate oxidative stress. Therefore, consumption of sesame seeds rich in lignans hopefully results in physiological activity to promote health.