To investigate the therapeutic effects and underlying mechanisms of Sorafenib in a rat model of HF (hepatic fibrosis). A total of 26 rats were randomly allocated into four groups: normal control, model, silymarin, and Sorafenib groups. Except for the normal control group, hepatic fibrosis was induced in all animals via carbon tetrachloride (CCl₄) administration. Following successful model establishment, the respective treatments were administered by gavage. Serum levels of ALT (alanine aminotransferase), AST (aspartate aminotransferase), HYP (hydroxyproline), LN (laminin), HA (hyaluronic acid), Col IV (type IV collagen), PCIII (procollagen type III), TNF-α (tumor necrosis factor-α), IL-17 (interleukin-17), IL-1β (interleukin-1β), and interleukin-6 (IL-6) were determined. Histopathological examination was performed to assess hepatic morphology and fibrosis severity. Immunohistochemistry was utilized to detect the expression of α-SMA (α-smooth muscle actin) and transforming TGF-β1 (growth factor-β1) in liver tissues. Additionally, Western blot analysis was conducted to evaluate the expression of pathway-associated proteins, including NF-κB (nuclear factor-κB) and VEGF (vascular endothelial growth factor). Compared with the model group, both silymarin and Sorafenib treatments significantly reduced serum levels of ALT, AST, HYP, TNF-α, IL-17, IL-1β, IL-6, PCIII, LN, HA, and Col IV. In liver tissues, the expression levels of TNF-α, α-SMA, hypoxia-inducible factor-1α (HIF-1α), VEGF, and phosphorylated NF-κB p65 were markedly decreased, whereas IκBα expression was significantly increased following treatment. Immunohistochemical analysis further confirmed that Sorafenib and silymarin significantly downregulated the expression of TGF-β1 and α-SMA compared to the model group. Sorafenib may alleviate hepatic inflammation, attenuate fibrosis, and improve liver function by inhibiting the activation of the TNF-α/NF-κB and HIF-1α/VEGF signaling pathways.