To investigate effects of eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on acute inflammation, we fed rats either of the following four diets: an EPA-rich diet for 5 or 15 days, a DHA-rich diet for 5 or 15 days, a control diet for 5 or 15 days, and standard chow for 15 days. At the end of diets, the carrageenan-induced swelling of footpads was measured. Peritoneal cells were analyzed for their fatty acids in the phospholipid fraction. The swelling was similarly reduced in the EPA and DHA groups (p < 0.05, if fed for 15 days) compared with rats fed the control diet for 15 days. The mean proportion of arachidonic acid (AA) to the sum of highly unsaturated fatty acids was correlated (r = 0.87) to the mean degree of swelling among all dietary groups (n = 7). Effects of EPA and DHA might be explained by the reduced availability of AA for eicosanoid formation represented by the proportion of AA.