A subcutaneous air pouch formed in Sprague-Dawley rats was used to study the effect of diets enriched in γ-linolenic acid (GLA) (in plant seed oil) and eicosapentaenoic acid (EPA) (in fish oil) on acute inflammation induced by monosodium urate crystals. The GLA-enriched diet suppressed significantly the cellular phase of inflammation (polymorphonuclear leukocyte accumulation, crystal phagocytosis, and lysosomal enzyme activity), but it had little effect on the fluid phase (exudate volume and protein concentration). In contrast, the EPA-enriched diet suppressed the fluid phase but not the cellular phase of inflammation. The findings indicate that the fluid and cellular phases of acute inflammation can be controlled independently. A combined diet of fish oil and plant seed oil (EPA-enriched and GLA-enriched) reduced both the cellular and fluid phases of inflammation. Thus, dietary provision of alternative substrates for oxidative metabolism (other than arachidonic acid) modifies monosodium urate crystal-induced acute inflammation.