Background: We have already reported an attenuating effect of a semipurified alcohol extract of soy protein (mainly consisting of isoflavones) on glomerular injury. Therefore, in the present study, we investigated whether soy protein itself has an ability to attenuate glomerular injury when added to casein diet in male Imai rats of a spontaneous focal segmental glomerulosclerosis model. Method: Male Imai rats were used and allocated into five groups. Group A of control casein diet (Ca) was fed standard diets containing 24.5% casein as a protein source. Group B of control soy protein diet (SP) was fed soy protein diet containing 24.5% protein that substituted a soy protein isolate for casein. Groups C (Ca-SP10) and D (Ca-SP20) were fed a mixture diet of casein (24.5%) and SP (10%) or SP (20%). Group E (Ca-Ca) was fed high casein diet containing the same quantity in protein content (44.5% casein) as the Ca-SP20 diet. Body weight, urinary protein, serum constituents and systolic blood pressure were investigated every 4 weeks from 12 weeks through 24 weeks of age. At 24 weeks of age, rats were studied morphologically. Results: Animals fed control SP diet showed a significantly greater body growth than animals fed the other 4 test diets. No significant differences were found in body growth among the other 4 groups except for group E, which showed a stunt at the end of the experiment. Control SP diet significantly decreased proteinuria and serum cholesterol and attenuated glomerular injury and glomerular hypertrophy as compared with control casein diet. Added SP failed to attenuate glomerular injury, but when compared with high casein diet (group E), added SP resulted in less proteinuria, less hyperlipidemia, less hypoalbuminemia, less glomerular hypertrophy and less renal histological damage despite the quantity being the same in protein content. Conclusion: The present study indicates that soy protein added to conventional casein diet did not have the ability to attenuate glomerular injury, but soy protein is not as harmful as casein as a protein source when added to casein diet in the development of glomerular injury in the rat model of spontaneous focal glomerular sclerosis.