We have previously shown that both n-3 (fish oil) and n-6 (soybean oil) PUFA-rich diets reduce carrageenan-induced paw edema in rats. The present study evaluated the role of corticosteroids, and the effect of indomethacin on this response. Basal (pre-carrageenan) levels of corticosterone were elevated in both lipid diets compared to the chow diet. During inflammation, corticosterone levels increased to a similar extent in the chow and lipid diets. With 2.0 mg/kg indomethacin, edema was reduced in the chow diet and the n-3 diet, while it was not changed in the n-6 diet. In contrast, the 16.6 mg/kg dose of indomethacin induced a mild increase in edema in the chow diet but a pronounced edema increase in the lipid diets. The increase in corticosterone levels induced by carrageenan was either reduced (chow) or completely abolished (lipids) by the treatment with the higher dose of indomethacin, compared to both the control (untreated) group, and the lower dose of indomethacin. These data indicate that both acute inflammation and the response to an antiinflammatory drug were attenuated by n-3 or n-6 PUFA-rich diets. They also showed that indomethacin can have anti- or proinflammatory properties reflecting the extent of the corticosterone inhibition by indomethacin.