Objective- The liver has a unique location in the body for performing multiple functions such as,metabolism, detoxification and synthesis. There are limitation for liver transplantation due to shortage ofavailable donors and requires for sophisticated technology and support surgical teams. The purpose of thisstudy was to investigate the hepatocyte transplantation into the spleen of animal model such as dog toestabli sh basic condition for further studies.Design- In vivo experimental Study.Animals- Five Iranian indigenous mixed breed dogs of both sexes, 15/8±3 months old and 19.6±8.2weighting were used in this sudy.Procedures- Ventral midline celiotomy was performed under general aneasthesia and liver sampls wereobtained using suction technique by a 50cc syring and 14 gauge needle . Then obtained samples wereinjected into the same dog 's spleen directly and also via splenic artery, the celiotomy incision sutured andthe animal left to recover. On the 16th postoperative day, under general anaesthesia, the gross apearance ofspleen were recorded and photographed and for histpathological evaluation, partial splenectomy wasperformed. The prepared sections were stained with Hemotoxylin Eosin [H& E] and Periodic Acid Schiff[PAS] and studied under light microscoy.Results- The gross evaluations ofthe removed spleen showed a whitish area at the injection site in all ofthe 5 transplanted dogs, spleen vessels had been dilated and enlarged in diameter. Microscopically thegroups of hepatocytes in the center of lymphoid follicles in the white pulp were noted.Conclusion and Clinical Relevance- Hepatocyte transplantation could be useful for both supporting anacute liver failure and for surviving as a bridge to liver tansplantation in terminal liver failure.