Compared with casein, dietary soy protein slows disease progression in animal models of chronic renal injury. To determine whether dietary soy protein feeding can alter early disease progression, male Han:SPRD-cy rats (n = 87) in a very early stage of chronic kidney disease were fed soy protein compared with casein-based diets for 1 or 3 wk. Kidneys were assessed for fibrosis, cyst growth, fatty acid composition and prostaglandin E2 (PGE2) production. Soy protein feeding significantly reduced renal fibrosis by 22% (P = 0.0347) and 38% (P = 0.0102) after 1 and 3 wk of diet, and cyst growth was 34% lower after 3 wk (P < 0.0001). Kidney 18:2(n-6) levels were reduced in normal and diseased rats after as little as 1 wk of consuming the soy protein diet. Dietary soy protein also partially ameliorated the suppression of PGE2 production observed in diseased kidneys. Compared with diseased kidneys from casein-fed rats, ex vivo PGE2 release was 31-32% higher after 1 (P = 0.0281) and 3 (P = 0.0189) wk of dietary soy protein consumption. Hence, the first signs of a beneficial soy protein effect were observed after 1 wk of feeding, with further improvements evident after 3 wk. These data demonstrate that dietary soy protein compared with casein delays disease progression in an early stage of chronic kidney disease. J. Nutr. 134: 1504-1507, 2004.