Objective To investigate whether the Isodon ternifolius ( D. Don ) Kudo attenuates carbon tetrachloride (CCl₄ )-induced liver fibrosis in rats by downregulating the nuclear transcription factor-κB (NF-κB) signaling pathway through interference with IκB-α phosphorylation. Methods Hepatic fibrosis was induced in rats with CCl₄ . Biochemical analysis was used to detect alanine aminotransferase (ALT) and hydroxyproline ( HYP), and the enzyme- linked immunosorbent assay was used to detect transforming growth factor (TGF-β1), α-smooth muscle actin (α-SMA), interleukin-6 (IL-6) and tumor necrosis factor-α ( TNF-α) levels in sera. Fluorescence quantitative PCR was used to detect Toll-like receptor 4 (TLR4), NF-κB p65, IκB-α mRNA expression, and Western blot were used to analyze TLR4, NF-κB p65, and phosphorylated (p)-IκB-α protein expression in rat liver tissues. Hematoxylin-eosin staining was used to evaluate histopathological damage in the rat livers. Results Compared with that in the model group, the pathological damage to the livers of rats treated with Isodon ternifolius (D. Don) Kudo extracts was ameliorated; the levels of ALT, HYP, TGF-β1, α-SMA, IL-6 and TNF-α in the serum of rats with liver fibrosis treated with Isodon ternifolius (D. Don) Kudo extracts were significantly reduced; the expression of TLR4 and NF-κB p65 mRNA were significantly inhibited; IκB- α mRNA was significantly upregulated; and the expression of TLR4, NF-κB p65 and p-IκB-α protein was downregulated. Conclusions Isodon ternifolius (D. Don) Kudon alleviated liver fibrosis by downregulating IκB-α phosphorylation and inhibiting activation of the NF-κB signaling pathway.