Objective    To explore the effects of low-protein diet supplemented with ketoacids on podocytes as well as local RAS in the kidney of patients with diabetic nephropathy. Methods    A tal of 61 patients with T2DN and CKD stages 3-4 were included. All the patients were randomly divided into two groups: low protein group (0.6 g•kg BW-1•d-1 and 30 kcal•kg BW-1•d-1, LPD) and LPD +Ketoacids (KA) group (0.6 g•kg BW-1•d-1, 30 kcal kg BW-1•d-1, and Ketoacids 100 mg•kg BW-1• d-1). Blood and 24 h urine samples were collected at baseline and every 3 months for routine examination to evaluate the efficacy of LPD + KA diet. Podocytes loss was evaluated by mRNA expression of nephrin, podocin, and synaptopodin in urine at baseline and every 3 months. Urinary angiotensinogen was detected by ELISA at baseline and every 3 months.  Results    After 12 months of follow-up, there were no significant difference statistically in declines of GFR between LPD and LPD+ KA group (P＞0.05). Compared with LPD group, proteinuria in LPD+KA group was decreased [(0.43± 0.35) vs (0.15±0.36) g/24 h, P＜0.01]. Patients in two groups were both in good nutritional condition, and KA independently increased the levels of serum albumin and prealbumin (all P＜0.05). The urinary angiotensinogen/creatinine ratio was correlated with GFR (r＝-0.437, P＝0.001), serum creatinine (r＝-0.733, P＝0.000) and proteinuria (r＝-0.851, P＝0.000); while urinary mRNA expression of podocyte markers (podocin and synaptopodin were correlated with proteinuria (r＝0.340, P＝0.012; r＝0.333, P＝0.014; respectively), but had no correlation with GFR and serum creatinine. After 12 months of follow-up, the urinary angiotensinogen/creatinine ratio in LPD+KA group was lower than in LPD group (P＜0.05). The mRNA expression of podocin and synaptopodin were lower in LPD+ KA group compared with LPD group in urinary sediment (P＜0.05). Further correlation analysis suggested that the change of urinary expression of podocin and synaptopodin had a modest but significant correlation with the change urinary angiotensinogen creatinine ratio change (r＝0.305, P＝ 0.026; r＝0.281, P＝0.04, respectively) after treatment for one year.  Conclusions    Low protein diet supplemented with Ketoacids (LPD + KA) is associated with amelioration of proteinuria, meanwhile nutrition status remains well. The mechanism of these effects may be explained by the role of LPD+KA diet in reducing urine podocyte loss and lowering the angiotensinogen level in the urine.