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Toll‐like receptor 7 (TLR7) signaling predominantly regulates production of type I interferons (IFNs), which has been suggested in clinical studies to be antifibrotic. However, the mechanistic role of the TLR7‐type I IFN axis in liver fibrosis has not been elucidated. In the present study, liver fibrosis was induced in wild‐type (WT), TLR7‐deficient, and IFN‐α/β receptor‐1 (IFNAR1)‐deficient mice and TLR7‐mediated signaling was assessed in liver cells isolated from these mice. TLR7‐deficient and IFNAR1‐deficient mice were more susceptible to liver fibrosis than WT mice, indicating that TLR7‐type I IFN signaling exerts a protective effect against liver fibrosis. Notably, the hepatic expression of interleukin‐1 receptor antagonist (IL‐1ra) was suppressed in TLR7‐ or IFNAR1‐deficient mice compared with respective WT mice, and treatment with recombinant IL‐1ra reduced liver fibrosis. In vivo activation of TLR7 …