Flaxseed has demonstrated useful antiinflammatory properties in a number of animal models and human diseases. We undertook a study to determine if flaxseed would also modify clinical course and renal pathology in the Han:SPRD-cy rat. Male Han:SPRD-cy rats were pair fed a 10% flaxseed of control rat chow diet for eight weeks from weaning. Tissue was harvested for analysis of cystic change, apoptosis, cell proliferation, and fibrosis. Tissue was also harvested for lipid analysis using gas chromatography. Animals thrived on both diets. Flaxseed-fed animals had lower serum creatinine (69 vs. 81 mumol/liter, P = 0.02), less cystic change (1.78 vs. 2.03 ml/kg, P = 0.02), less renal fibrosis (0.60 vs. 0.93 ml/kg, P = 0.0009), and less macrophage infiltration (13.8 vs. 16.7 cells/high-power video field) of the renal interstitium than controls. The groups did not differ in renal tubular epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids (total omega 6:omega 3 ratio 3.6 vs. 9.1, P < 0.0001). Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids.