To evaluate the effect of aldosterone (ALD) and spironolactone (SPI, one of the aldosterone receptor antagonists) on synthesis and secretion of fibronectin (FN) and expression of transforming growth factor-beta1 (TGF-beta1) mRNA in cultured rat mesangial cells.(1) Mesangial cells were treated with medium containing different concentrations of ALD (10(-11), 10(-9), 10(-7) mol/L) and/or 10(-7) mol/L SPI for 48 h, while control cells were treated with vehicle only. The levels of FN in the supernatants were measured by ELISA method. The expressions of FN mRNA and TGF-beta1 mRNA were detected by semi-quantitative RT-PCR. (2) Mesangial cells were treated with 10(-9) mol/L ALD for 24, 48, 72 h. The levels of FN in the supernatants were measured by ELISA method. The expressions of FN mRNA and TGF-beta1 mRNA were detected by semi-quantitative RT-PCR.ELISA method showed that the level of FN in the supernatant of cultured rat mesangial cells stimulated with ALD increased significantly in a dose- and time-dependent manner. Also the expressions of FN mRNA and TGF-beta1 mRNA were increased significantly by ALD in a dose- and time-dependent manner by semi-quantitative RT-PCR. SPI inhibited the stimulating effect of ALD on synthesis of FN and expressions of FN mRNA and TGF-beta1 mRNA in cultured rat mesangial cells.ALD up-regulates the protein synthesis and mRNA expression of FN, and up-regulates the mRNA expression of TGF-beta1 in cultured rat mesangial cells. SPI inhibits the effect of ALD, and thus implication in the treatment of Glomerulosclerosis.