Aims. Proteinuria and transforming growth factor β (TGF-β) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-β. Aldosterone may not be inhibited with angiotensin-converting enzyme inhibitors (ACEIs) andor angiotensin receptor blockers (ARBs) due to aldosterone escape. We aimed to evaluate the effect of spironolactone on parameters leading to fibrosis. Methods. This prospective study included 30 non-diabetic chronic kidney disease (CKD) patients treated with ACEIs andor ARBs. The patients were divided into two groups that are similar in terms of demographic parameters. 25 mg of spironolactone was added to group 1 (n 15) for six months, though it was not administered to group 2 (n 15). Creatinine (U-Cr), protein (U-Prot), and TGF-β1 (U-TGF-β1) were measured in spot urine sample in the beginning of study and six months later. Results. Twenty-four patients completed the study. There were no significant changes in mean blood pressure, glomerular filtration rate, creatinine, albumin, and plasma aldosterone concentrations during the observation period in either group. U-ProtU-Cr (mg/mg Cr) was reduced from 2.43 ± 4.85 at baseline to 1.66 ± 3.51 at sixth month (p 0.003) in group 1. In addition, U-TGF-β1U-Cr (ng/mg Cr) was also reduced from 22.50 ± 6.65 at baseline to 17.78 ± 10.94 at sixth month (p 0.041) in the same group. U-TGF-β1/U-Cr and U-Prot/U-Cr ratios after the sixth month were not found significant compared with baseline values in group 2. Conclusion. Spironolactone reduced both proteinuria and urinary TGF-β1 excretion in CKD patients. We consider that spironolactone would be beneficial to prevent progression of renal fibrosis in CKD. © 2009 Informa UK, Ltd.