Background　Although　it　has　been　preclinically　suggested　that　adipose　tissue-derived　mesenchymal　stem　cell　(ADSC)-based　therapy　could　effectively　treat　chronic　liver　diseases,　the　hepatic　engraftment　of　ADSCs　is　still　extremely　low,　which　severely　limits　their　long-term　efficacy　for　chronic　liver　diseases.　This　study　was　designed　to　investigate　the　impact　of　antioxidant　preconditioning　on　hepatic　engraftment　efficiency　and　therapeutic　outcomes　of　ADSC　transplantation　in　liver　fibrotic　mice.　Methods　Liver　fibrosis　model　was　established　by　using　intraperitoneal　injection　of　carbon　tetrachloride　(CCl4)　in　the　male　C57BL/6　mice.　Subsequently,　the　ADSCs　with　or　without　antioxidant　pretreatment　(including　melatonin　and　reduced　glutathione　(GSH))　were　administrated　into　fibrotic　mice　via　tail　vein　injection.　Afterwards,　the　ADSC　transplantation　efficiency　was　analyzed　by　ex　vivo　imaging,　and　the　liver　functions　were　assessed　by　biochemical　analysis　and　histopathological　examination,　respectively.　Additionally,　a　typical　hydrogen　peroxide　(H2O2)-induced　cell　injury　model　was　applied　to　mimic　the　cell　oxidative　injury　to　further　investigate　the　protective　effects　of　antioxidant　preconditioning　on　cell　migration,　proliferation,　and　apoptosis　of　ADSCs.　Results　Our　data　showed　that　antioxidant　preconditioning　could　enhance　the　therapeutic　effects　of　ADSCs　on　liver　function　recovery　by　reducing　the　level　of　AST,　ALT,　and　TBIL,　as　well　as　the　content　of　hepatic　hydroxyproline　and　fibrotic　area　in　liver　tissues.　Particularly,　we　also　found　that　antioxidant　preconditioning　could　enhance　hepatic　engraftment　efficiency　of　ADSCs　in　liver　fibrosis　model　through　inhibiting　oxidative　injury.　Conclusions　Antioxidant　preconditioning　could　effectively　improve　therapeutic　effects　of　ADSC　transplantation　for　liver　fibrosis　through　enhancing　intrahepatic　engraftment　efficiency　by　reducing　oxidative　injuries.　These　findings　might　provide　a　practical　strategy　for　enhancing　ADSC　transplantation　and　therapeutic　efficiency.