Obesity‐related kidney disease should be prevented or retarded. We aimed to investigate whether early treatment with enalapril ameliorates later renal injury induced by early postnatal overnutrition. Three or ten male pups per mother were assigned to either the Obese or Lean group during the first 21 days of life. These pups were treated with enalapril (Obese enalapril, OE; Lean enalapril, LE) or vehicle (Obese control, OC; Lean control, LC) for 15–28 days. Body weight, blood pressure (BP), and renal alterations were determined at 3 months. Enalapril decreased body weight only in the Lean group at 3 months (P < 0.05). Systemic BP levels were higher in the LE, OC, and OE groups than in the LC group at 3 months (P < 0.05). Fewer glomeruli per section area were found in the LE, OC, and OE groups than in the LC group and in the OE group than in the OC group (P < 0.05). The LE and OE groups had higher index scores of glomerulosclerosis and tubulointerstitial fibrosis than the controls (P < 0.05). LE pups showed increased intrarenal angiotensin II receptor type (AT)2 and matrix metalloproteinase (MMP)‐9 and decreased renin and tissue inhibitor of MMP (TIMP)‐1 expression than the LC rats (P < 0.05). OE pups showed increased intrarenal AT2 and decreased AT1 and TIMP‐1 expression than the OC rats (P < 0.05). In conclusion, early treatment with enalapril can induce detrimental renal effects in later life and may not be renoprotective in programmed obese adult rats. J. Cell. Physiol. 232: 447–455, 2017. © 2016 Wiley Periodicals, Inc. Early treatment with enalapril in neonatally overfed rats resulted in decreased glomerular number, increased glomerulosclerosis and tubulointerstitial fibrosis, and dysregulated intrarenal AT1, AT2, and TIMP‐1 expressions later in life. Compared to the Lean control rats, neonatally overfed adult rats were overweight and had hypertension and glomerulosclerosis with a fewer number of glomeruli, regardless of enalapril administration. Moreover, enalapril treatment in Lean rats after the nephrogenic period led to systemic hypertension and progressive renal injury with a low nephron number later in adulthood.