Dietary protein restriction slows the progression of established diabetic nephropathy (DN). In contrast, the role of protein intake (PI) in the pathogenesis of early DN is unknown. The aim of this study was to examine the relationship between PI and markers of early DN, specifically kidney volume(KV), glomerular filtration rate (GFR) and albumin excretion rate (AER), in children and adolescents with type 1 diabetes. The study cohort included 145 subjects (72 males; 13.2 1 3.5 yr) with diabetes for 5-10 yr, divided into 3 groups based on pubertal duration. KV was measured by ultrasound and corrected for body surface area (BSA). Serum creatinine and sodium-lithium countertransport (NaLi) were measured. Median AER and mean creatinine and urea excretion rates were calculated from three 24h urine collections. Dietary PI was calculated by: (UUN + NUN) × 6.25, (UUN-urinary urea nitrogen; NUN-non-urea nitrogen (31 mg/kg/d)). GFR was estimated by creatinine clearance, standardized for BSA. Mean HbA1c was 8.8 1 1.4%. Mean PI for the whole group was 1.22 1 0.04 g/kg/d (X 1 SE). Mean PI was 1.49 g/kg/d (95% CI 1.37-1.61) in prepubertal subjects, 1.12 g/kg/d (95% CI 1.02-1.22) in midpubertal subjects, and 0.98 g/kg/d (95% CI 0.86-1.10) in postpubertal subjects. Mean PI was significantly higher (p<0.0001) in males (1.41 g/kg/d; 95% CI 1.31-1.51) than females (1.02 g/kg/d; 95% CI 0.94-1.10). PI was related to GFR (p<0.0001), but not AER, KV, HbA1c or NaLi in univariate analysis. In multiple regression analysis with PI as the dependent variable and GFR, KV, AER, NaLi, sex, age, pubertal duration, HbA1c and BSA as independent variables, PI was significantly positively associated with GFR(p<0.0001) and male sex (p<0.0001) and negatively associated with BSA(p=0.001) and age (p=0.01). In this cross-sectional study, we failed to show a significant relationship between PI and early markers of DN other than GFR. However, the possibility that PI affects the onset or progression of early DN cannot be ruled out without a prospective study.