NF-κB modulates coding genes for adaptive, innate immunity and inflammation. Some toxins activates α smooth muscle actin (α SMA), a marker of kidney myofibroblast, which is enhanced by Smads over expression. The current study estimated the efficacy of silymarine (SIL) in combination with dandelion (DA) and (-)-epigallocatechin-3-gallate (EGCG) against kidney damage induced via CCl4 in rats. This is demonstrated by the suppression of α-SMA, Smad-2 and NF-κB protein expressions in renal tissue. CCl4 was injected as a single intraperitoneal dose, followed by one month treatment with SIL, DA and EGCG. Serum urea and creatinine levels were significantly increased upon CCl4 intoxication whereas, uric acid level was slightly affected compared to the control values. Immunohistochemical analysis of kidney sections revealed that CCl4 induced an increase in immune response of NF-κB, α-SMA and Smad-2 protein expressions. While, treatment with the aforementioned natural products either alone or in combination showed mild immune reactivity in blood vessels and glomeruli with the combination regimen of the three antioxidants showing the most significant effect. This was also confirmed by histopathological examinations.