Although persistent proteinuria is characteristic of diabetic nephropathy (DN), it is important to differentiate non-diabetic renal diseases (NDRD) in diabetic patients with proteinuria. In order to re-evaluate the indications for renal biopsy in the diabetic patients, we retrospectively analyzed the relationship between clinical features and histological diagnosis in 97 Japanese patients with type 2 diabetes manifesting overt proteinuria. Renal biopsy was performed because they were clinically suspected to have NDRD. Patients were divided into three groups according to the histological diagnosis: (1) the DN group (n=35) had only diabetic lesions, (2) the complicated group (n=16) had histological changes of NDRD superimposed on DN and (3) the non-DN group (n=46) had NDRD without diabetic lesions. We evaluated the specificity and sensitivity of four clinical parameters (duration of diabetes, presence or absence of diabetic retinopathy, microscopic hematuria and granular casts as urinary sediments) for the prediction of NDRD. Short duration of diabetes (<5 years) showed high sensitivity (75%) and specificity (70%). Diabetic retinopathy showed the highest sensitivity (87%) and specificity (93%). The sensitivity and specificity of microscopic hematuria (56 and 58%) and granular casts (68 and 47%) were lower. Our study confirmed that the absence of retinopathy and short duration of diabetes are useful clinical indications for renal biopsy in diabetic patients with overt proteinuria.