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We have previously demonstrated that both n–3 and n–6 polyunsaturated fatty acids (PUFA)-rich diets decrease the acute inflammatory response partially explained by the high corticosterone basal levels. The present study aimed to determine the effect of hyperlipidic diets (PUFA n–3 or n–6) on phagocytosis, hydrogen peroxide (H2O2) and nitric oxide (NO) release by macrophages, bradykinin (BK) and NO release in the paw inflammatory perfusate and Kallikrein (KK), corticosterone and leptin blood levels. Hyperlipidic diets decreased H2O2 release from macrophages stimulated by carrageenan or phorbol-miristate-acetate (PMA), NO release from macrophage stimulated by carrageenan, BK and NO release in the edema perfusate, KK plasma levels and the increase of serum leptin after carrageenan stimulus. These data show that both fish and soybean oil-rich diets promote similar alterations on inflammatory mediators of carrageenan edema and a causal association with the anti-inflammatory effect of these diets.