OBJECTIVE As interleukin-6 (IL-6) has an important role in general metabolism with high circulating levels in obesity and other associated diseases, the factors regulating its synthesis and release have been considered possible therapeutic targets and have recently been studied. We examined the influence of three different diets, each having a different fatty acid composition--saturated, monounsaturated or polyunsaturated (coconut oil, olive oil and sunflower oil diets), on IL-6 release from rat adipocytes, and the interaction between diet and other regulatory factors of IL-6 release, such as epinephrine. METHODS A group of rats was assigned to one of the three different diets, each with a significantly different concentration of saturated, monounsaturated and polyunsaturated fatty acids. Samples were taken from the omental adipose tissue for measurement of the triacylglycerol fatty acid composition of the tissues and for adipocyte isolation. IL-6 release from adipocytes was measured in vitro, under nonstimulated conditions and also with two concentrations of epinephrine in the medium. RESULTS Animals fed with the olive oil diet showed lower values of IL-6 release with and without epinephrine stimulation. IL-6 release from adipocytes varied according to the diet, but not according to epinephrine dose. However, a significant interaction was found between the epinephrine dose and the diet in IL-6 release regulation. CONCLUSIONS IL-6 release from adipocytes was markedly regulated by the dietary fatty acid composition, even under epinephrine stimulation, with lower values of IL-6 release in the olive oil diet. The study also showed that epinephrine regulation of IL-6 release was related to the diet.