Background/Aim: Five-sixths-nephrectomized rats present renal functional and histological abnormalities which are attenuated by enalapril treatment. c-Jun N-terminal kinase (JNK), a mitogen-activated protein kinase, and nuclear factor-ĸB (NF-ĸB) pathways can be activated by angiotensin II which has been implicated in renal injury. The aim of this study was to investigate the effect of enalapril on the expression of NF-ĸB and JNK in renal cortices of five-sixths-nephrectomized rats. Methods: Of the 65 rats studied, 25 underwent five-sixths nephrectomy and received no treatment, 15 underwent five-sixths nephrectomy and received enalapril, 15 were sham operated and received no treatment, and 10 were sham operated and received enalapril. On postoperative days 15 and 90, systolic blood pressure, glomerular filtration rate, and albumin excretion were determined. The rats were then killed and the kidneys removed for histology and immunohistochemistry. Results: In five-sixths-nephrectomized rats, we observed functional and structural renal alterations, as well as greater NF-ĸB/JNK expression and higher macrophage counts. Enalapril treatment reduced all of these changes. Conclusion: The protective effect of enalapril on the kidney of five-sixths-nephrec tomized rats might be related to the inhibition of NF-ĸB and JNK activation.