As　an　intercellular　signaling　molecule,　Hedgehog　(Hh)　plays　a　critical　role　in　liver　fibrosis/regeneration.　Transcription　effectors　Gli1　and　Gli2　are　key　components　of　the　Hh　signaling　pathway.　However,　whether　inhibition　of　Gli1/2　activity　can　affect　liver　fibrogenesis　is　largely　unknown.　In　the　present　study,　we　investigated　the　effect　of　Gant61　(a　Gli1/2　transcription　factor　inhibitor)　on　liver　fibrosis　and　its　possible　mechanism.　Wild-type　and　Shh-EGFP-Cre　male　mice　were　exposed　to　CCl＜sub＞4＜/sub＞,　and　then　treated　with　or　without　Gant61　for　four　weeks.　The　level　of　liver　injury/fibrosis　and　expression　levels　of　mRNA　and　protein　related　to　the　Hh　ligand/pathway　were　assessed.　In　our　study,　CCl＜sub＞4＜/sub＞　treatment　induced　liver　injury/fibrosis　and　promoted　activation　of　hepatic　stellate　cells　(HSCs).　In　addition,　CCl＜sub＞4＜/sub＞　induced　the　expression　of　Shh　ligands　in　and　around　the　fibrotic　lesion,　accompanied　by　induction　of　mRNA　and　protein　expression　of　Hh　components　(Smo,　Gli1　and　Gli2).　However,　administration　of　Gant61　decreased　liver　fibrosis　by　reduction　in　HSC　number,　down-regulation　of　mRNA　and　protein　expression　of　Hh　components　(Smo,　Gli1　and　Gli2),　and　cell-cycle　arrest　of　HSCs.　Our　data　highlight　the　importance　of　the　Shh　pathway　for　the　development　of　liver　fibrosis,　and　also　suggest　Glis　as　potential　therapeutic　targets　for　the　treatment　of　liver　fibrosis.