The roots of Coleus vettiveroides (CV) have been traditionally used in Indian medicinal systems such as Ayurveda and Siddha for its antioxidant, anti‐inflammatory, and antidiabetic effects. This study examines the antifibrotic potential of CV ethanolic root extract (CVERE) against thioacetamide (TAA)‐induced liver fibrosis in Wistar rats. TAA was administered via i.p., thrice weekly for 11 weeks to induce liver fibrosis in rats. In separate groups, rats were administered with TAA and were concurrently treated with CVERE 125 mg/kg, CVERE 250 mg/kg, and silymarin (SIL) 100 mg/kg. Liver marker enzymes of hepatotoxicity, oxidative stress markers, proinflammatory marker gene expression (TNF‐α, NF‐κB, COX, and ILs), fibrotic marker gene expression (collagen I and III), immune histochemical expression of fibrosis marker proteins, and histopathologic changes were analyzed. TAA administration led to a significant (p < 0.001) increase in the serum level of hepatotoxic marker enzymes. The TAA‐treated group showed higher levels (p < 0.001) of MDA and reduced activities of SOD and CAT in the liver. TAA administration increased CYP2E1 expression, proinflammatory, and fibrotic marker gene expressions in rat liver. The histopathology of the liver confirms TAA‐induced architectural distortion and fibrotic changes. CVERE and SIL simultaneous treatments significantly protected against TAA‐induced oxidative stress, inflammation, and liver fibrosis. In conclusion, CVERE inhibited TAA‐induced liver fibrosis through downregulation of TAA metabolic activation, redox imbalance, and inflammation through repression of the NF‐κB pathway.
