Eicosapentaenoic acid (EPA) is an n-3 polyunsaturated fatty acid (PUFA) found in fish oil. We recently showed that docosahexaenoic acid (DHA), another n-3 PUFA, potently inhibited pig basilar and coronary artery contractions induced by U46619 (a TP receptor agonist) and prostaglandin (PG) F. We also showed that prostanoid TP receptors are potential targets for DHA. In this study, we investigated whether EPA, like DHA, suppresses contractions of pig basilar and coronary arteries induced by U46619 and PGF through inhibition of the TP receptor. EPA suppressed both U46619- and PGF-induced pig basilar and coronary contractions in a concentration-dependent manner without affecting 80 mM KCl-induced contractions. U46619-/PGF-induced contractions in both arteries were completely/largely suppressed by SQ 29,548 (a TP receptor antagonist). In addition, EPA suppressed U46619-/PGF-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in human TP receptor-overexpressing 293T cells, whereas it showed only a slight effect on PGF-induced [Ca2+]i increases in human FP receptor-overexpressing 293T cells. These findings suggest that EPA strongly suppresses TP-receptor-mediated contractions of pig basilar and coronary arteries, which can be partially attributed to its inhibitory effects on the TP receptor.