Liver fibrosis is a prevalent liver disease that requires rapid and effective treatment prior to its progression to cirrhosis and liver damage. Recently, several reports have investigated the efficacy of phytotherapy using natural herbal extracts rather than synthetic drugs to treat several liver diseases. Policosanol is a herbal extract used to treat patients with cardiovascular. However, its therapeutic effect on liver fibrosis is still unknown. Therefore, the present study aimed to assess the potential antifibrotic effect of policosanol compared to silymarin and the possible underlying molecular mechanisms. Rats were categorized into four groups; negative control group "NCG", the fibrotic group "FG", silymarin treated group "STG", and policosanol treated group "PTG". Serum liver enzymes, oxidative stress markers, angiogenic growth factors, and pro-inflammatory cytokines were measured biochemically. The relative mRNA expressions of liver caspase-3 and alpha-smooth muscle actin (α-SMA) were assessed. Immunohistochemical staining was carried out using anti- α-SMA, and anti-caspase-3 antibodies. Compared to NCG, the FG group demonstrated a significant decrease in the level of serum liver enzymes "GSH, TAC, and SDF. Nevertheless, it demonstrateda significant increase in the level of pro-inflammatory cytokines "Il-6, TNF"; oxidative stress markers "NO, MDA", and angiogenic growth factors "VEGF and PDGF" and the expression of α-SMA, and Caspase-3. Interestingly, the values of these measurements were restored to normal levels in the treated groups, particularly the PTG. In conclusion, our data revealed the beneficial effects of co-administration of policosanol or silymarin on the fibrotic liver rat model and thus could be a promising natural therapeutic drug.