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AIM: To investigate the influence of immune toleranceinduced by intrauterine exposure to fetal hepatocytes onliver transplantation in the adult rat.METHODS: LOU/CN rat fetal hepatocytes were injectedinto the fetuses of pregnant CHN rats (14-16 days ofgestation). At 7-9 weeks of age, the surviving male ratsreceived orthotopic liver transplantation (OLT) from maleLOU/CN donors and the survival period was observed andmonitered by mixed lymphocyte reaction assay andcytotoxicity test.RESULTS: (1) A total of 31 pregnant CHN rats with 172fetuses received fetal hepatocytes from LOU/CN rats viaintrauterine injection. Among them, thirteen pregnant ratsshowed normal parturition, with 74 neonatal rats growingup normally. (2) The mean survival period after OLT in ratswith fetal exposure to fetal hepatocytes was 32.1±3.7 days,which was significantly different from the control (11.8±2.3days, P＜0.01) in rats without fetal induction of immunetolerance. (3) Mixed lymphocyte proliferation assays yieldedremarkable discrepancies between the groups of rats with- orwithout fetal exposure to fetal hepatocytes, with values of8 411±1 361 and 22 473±1 856 (CPM±SD, P＜0.01) respectively.(4) Cytotoxicity assays showed values of 21.2±6.5 % and64.5±7.2 % (P＜0.01) in adult rats with or without fetalinduction of immune tolerance.CONCLUSION: Intrauterine injection of fetal hepatocytes intorat fetuses can prolong the survival period of liver transplantadult male rats recipients, inducting immune tolerance in OLT.