BACKGROUND: Bone marrow-derived macrophages (BMDMs) regulate hepatic progenitor cells (HPCs) differentiation, potentially via the Wnt signaling pathway. While M1-polarized BMDMs (M1-BMDMs) exert anti-fibrotic effects in the liver, Wnt5a is implicated in fibrosis progression. The specific influence of Wnt5a levels within M1-BMDMs on HPCs fate and cirrhosis development remains unclear. This study aimed to elucidate the relationship between M1-BMDM-derived Wnt5a and HPCs differentiation during cirrhosis progression. METHODS: First, Wnt5a protein expression was assessed in liver biopsy tissues from patients with hepatitis B-associated liver fibrosis. Second, cirrhosis was induced in rats using CCl(4)/2-AAF. In week 9, rats received intravenous injections of M1-BMDMs with Wnt5a knockdown (M1-BMDM (Wnt5a−KD)) or overexpression (M1-BMDM (Wnt5a−OE)); peripheral BMDMs recruitment was blocked using a CCR2 inhibitor. Fibrosis progression, ductular reaction (DR), and HPC differentiation were evaluated. In vitro, WB-F344 cells subjected to frizzled 2 (Fzd2) knockdown (WB-F344 (Fzd2−KD)) or overexpression (WB-F344 (Fzd2−OE)) were cultured with conditioned medium from M1-BMDM (Wnt5a−KD) (CM (Wnt5a−KD)) or M1-BMDM (Wnt5a−OE) (CM (Wnt5a−OE)). RESULTS: In patients with hepatitis B-related fibrosis, hepatic Wnt5a expression increased progressively with METAVIR fibrosis grade. In the rat cirrhosis model, M1-BMDMs (Wnt5a−KD) attenuated fibrosis, whereas M1-BMDMs (Wnt5a−OE) exacerbated it. Mechanistically, in vivo injection of M1-BMDMs (Wnt5a−KD) significantly inhibited HPCs differentiation into biliary epithelial cells (BECs), while M1-BMDM (Wnt5a−OE) promoted this differentiation. In vitro, CM (Wnt5a−KD) inhibited the differentiation of WB-F344 cells into BECs; this inhibition was potentiated by Fzd2 knockdown in WB-F344 cells but abrogated by Fzd2 overexpression. Conversely, under CM (Wnt5a−OE) conditions, WB-F344 (Fzd2−OE) cells exhibited increased cholangiocytic differentiation, an effect largely negated by Fzd2 knockdown. CONCLUSIONS: M1-BMDMs (Wnt5a−KD) demonstrated superior therapeutic efficacy against cirrhosis compared to unmodified M1-BMDMs. Wnt5a/Fzd2 signaling mediated the crosstalk between M1-BMDMs (Wnt5a−KD) and HPCs, revealing a novel therapeutic target for cirrhosis treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-025-01467-x.