Background/Aims: A diet rich in polyunsaturated Ω3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short– and long–term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. Methods: Eight rats each were pairfed FO– versus cholesterol–enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2–week trial: 1 rat on the FO and 1 rat on the control diet; 32–week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. Results: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75±2.19 vs. 6.87±1.91 ml/min/g, p<0.05), and the prostaglandin E₂/thromboxane B₂ ratio shifted towards the vasodilatative prostaglandin E₂ (1.76±0.18 vs. 0.91±0.19, p<0.05). During the long–term trial proteinuria in the FO animals progressed faster and to a higher level (176.5±32.2 vs. 82.7±36.7 mg/24 h at week 32, p<0.01). After 32 weeks the renal blood flow was significantly lower in th FO group 2.8±1.1 vs. 4.6±1.9 ml/min/g, (p<0.05), and the rats had an accelerated development of nephrosclerosis, with sclerotic lesions in 60.3±6.6% of the glomeruli as compared with 46.5±9.8% in the cholesterol and 39.8±5.9 in the control group (p<0.05). Conclusion: The short–time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.