We previously demonstrated the preventive effect of sesamin, a lignan from sesame oil, on the development of several experimental models of hypertension. In the present study, we explored the mechanisms underlying the antihypertensive effect of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive model. After a 5-week treatment period, aortic superoxide (O2-) production was measured in the lucigenin chemiluminescence assay. Chemiluminescence signals significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive rats compared with those in the normal diet-fed DOCA-salt rats, although the signals in sham-operated control animals were not affected by the sesamin feeding. In addition, there was a positive correlation between systolic blood pressure and aortic O2- production. These findings suggest that sesamin feeding inhibits enhanced vascular O2- production in DOCA-salt hypertensive rats and that the antioxidative action of sesamin may contribute to its antihypertensive activity.