OBJECTIVE: It is not known whether endothelial factor-1 (ET-1) and nitric oxide (NO) are involved in glomerulosclerosis. This study aimed at studying the changes and roles of ET-1 and NO in the process of glomerulosclerosis and the effects of the angiotensin converting enzyme inhibitor (ACEI), benazepril, and the angiotension Ⅱ receptor type Ⅰ antagonist, losartan. METHODS: Glomerulosclerosis was induced in rats by resecting one side of the kidneys and injecting adriblastine. The rats were randomly assigned into a glomerulosclerosis group (D group), a benazepril-treated glomerulosclerosis group (DB group), and a losartan-treated glomerulosclerosis group (DL group), 10 per group. Ten rats were sham-operated (Control group) and were injected with normal saline into caudal veins. After 6 weeks of benazepril or losartan administration, the mRNA expressions of ET-1 and iNOS in renal cortex were measured by reverse transcription polymerase chain reaction (RT-PCR). The protein levels of ET-1 and iNOS in renal cortex were detected by Western blotting, and the renal tissue Collagen Ⅳ and fibronectin were measured by immunohistochemistry. RESULTS: By the 4th week of adriblastine administration, urinary protein, serum cholesterol and blood urea nitrogen increased, while serum albumin decreased in Group D compared with those of the Control group (all P< 0.05). RT-PCR and Western blotting demonstrated that the mRNA and protein expressions of ET-1 increased 3.58 and 2.83 times, and the mRNA and protein expressions of iNOS increased 4.28 and 3.15 times in the renal cortex of the Group D when compared with those of the Control group. The expressions of Collagen Ⅳ and fibronectin also significantly increased in Group D. After 6 weeks of benazepril or losartan treatment, the deposition of extracellular matrix in the Groups DB and DL was significantly reduced and mRNA and protein expressions of ET-1 and iNOS had decreased compared with those of the Group D. Meanwhile, the expressions of Collagen Ⅳ and fibronectin also decreased in the two treatment groups. CONCLUSIONS: ET-1 and NO may participate in the process of glomerulosclerosis. Inhibition of ET-1 and iNOS blocks accumulation of extracellular matrix, and may avert glomerulosclerosis.