Eicosapentaenoic acid (EPA) can induce a shift in prostaglandin and leukotriene synthesis. The effects of EPA supplementation of the diet on the progression of chronic renal failure (CRF) were evaluated in a model of 5/6 renal mass ablation in rats. After 30 or 60 days of CRF, elevation in single-nephron glomerular filtration rate due to an increase in glomerular plasma flow and hydraulic pressure was observed. These hemodynamic alterations were followed by a rise in proteinuria and glomerular sclerosis. EPA treatment for 30 or 60 days did not substantially modify the hemodynamic or morphological profiles induced by renal mass ablation. In the present non-immune model of CRF, preglomerular vasodilation with glomerular hyperperfusion and hypertension were responsible, at least in part, for the presence of proteinuria and glomerular sclerosis. No additional vasodilation was observed in the present model of CRF, and, thus, hemodynamic effects induced by EPA did not modify renal damage, in contrast to the EPA effects observed in immune-mediated models of CRF.