Abstract: OBJECTIVE To observe the inhibitory effects of Liuwei Dihuang Pills(LWDHP) on macrophages activation in CCl₄-induced liver fibrosis in mice. METHODS C57BL/6 mice were induced liver fibrosis by CCl₄ exposure and administered with LWDHP for 6 weeks simultaneously. Liver tissue was investigated by HE and Sirius red staining. α-SMA was analyzed by immunofluorescence， qPCR and Western blot. Liver macrophages were observed by immunohistochemistry of CD68. The pro-inflammatory cytokines and chemokine such as TNF-α， IL-1β， CXCR3 and MCP1 were detected by qPCR or Western blot analysis. RESULTS After 6 weeks of CCl₄ administration， the expression of α-SMA significantly increased， and LWDHP potently inhibited the α-SMA expression. Immunohistochemistry showed that the expression of CD68 was very weak in normal group， CD68 was distributed mainly between fibrotic septa with strong positive expression in CCl₄ model group; Real-time quantitative PCR showed that TNF-α， IL-1β， MCP1 and CXCR3 expression significantly increased in model group compared with normal group. Compared with the model group， LWDHP significantly reduced the expression of CD68， inflammatory factors and chemotactic factors. CONCLUSION LWDHP shows a potent inhibition of macrophage activation in CCl₄-induced liver fibrosis.