Abstract： Objective To study the molecular mechanisms of hepatoeyte regeneration following different cold preservation (CP) durations after rat partial liver transplantation. Methods Mate inbred Lewis rats were used as donors and recipients. Donor liver was kept in 4℃ UW solution for 1 h (coldisehemia 1 h group, CI 1 h group), 8 h (CI 8 h group) and 16 h (CI 16 h group) and then implantedorthotopieally. 50% liver graft transplantation model was established by ligating the left portion ofmedian lobe, left lateral lobe and caudate lobe with 3-O silk suture prior to reperfusion. Survival rate ofeach group and hepatoeyte regeneration were recorded after grafting. Reverse transcription-polymerasechain reaction was used to detect the expression of IL-6 and TNF-α in the liver tissues. Western blotanalysis was done to measure STAT3 activation in the liver. Immunohistoehemistry was conducted toanalyze the expression of cyclin D1 and hepatocyte replication with BrdU uptake in the graft. ResultsOperative success rate in all groups was 100%. Compared with CI 1 h group, the TNF-α and IL-6expression (F=67.45 for TNF-a comparison, P<0.05 and F=287.73 for IL-6 comparison,P<0.05 respectively) in 8 h CI and 16 h CI groups was markedly increased after partial grafttransplantation. STAT3 activity in 8 h C1 and 16 h C1 groups was also significantly increased ascompared with that in 1 h CI group. Cyclin D1 expression in 8 CI group was demonstrated withcytoplasmic and nuclear staining at 24 h after transplantation. Grafts in 16 h CI group showed largeareas with no cyclin D1 expression. Number of hepatocytes with BrdU positively stained neclei in 8 hCI group was more than that in 16 h C1 group at 24 h after transplantation (t=19.40, P<0.05).Conclusion Hepatocytes regeneration was present following rat partial transplantation in the graftspreserved for limited time, which may be regulated by TNF-α/IL-6' STAT3/ Cyelin D1/DNAsynthesis pathways; Hepatocytes could not respond to early signals for liver graft regeneration when50%liver graft preserved for 16 h.