Lycium barbarum polysaccharides (LBPs) have multiple biological and pharmacological functions, including antioxidant, anti-inflammatory and anticancer activities. This research was conducted to evaluate whether LBPs could alleviate carbon tetrachloride (CCl₄)-induced liver fibrosis and the underlying signaling pathway mechanism. Fifty male wistar rats were randomly allocated to five groups (n = 10): control, CCl₄ and CCl₄ with 400, 800 or 1600 mg/kg LBPs, respectively. Each wistar rat from each group was used for blood and tissue collections at the end of experiment. The results showed that CCl₄ induced liver fibrosis as demonstrated by increasing histopathological damage, α-smooth muscle actin expression, aspartate transaminase activities, alkaline phosphatase activities and alanine aminotransferase activities. LBPs supplementation alleviated CCl₄-induced liver fibrosis as demonstrated by reversing the above parameters. In addition, CCl₄ treatment induced the oxidative injury, increased the mRNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-1β, and up-regulated the protein expressions of toll-like receptor 4 (TLR4), TLR2, myeloid differentiation factor 88, nuclear factor-kappa B (NF-kB) and p-p65. LBPs supplementation alleviated CCl₄-induced oxidative injury, inflammatory response and TLRs/NF-kB signaling pathway expression by reversing the above some parameters. These results suggest that the alleviating effects of LBPs on CCl₄-induced liver fibrosis in wistar rats may be through inhibiting the TLRs/NF-kB signaling pathway expression.