Objective To investigate the relationship between 5-HT immunoreactive (5-HT-IR) endocrine cells and mast cells (MCs) in gastrointestinal tract and liver with liver regeneration. Methods One hundred and fifty adult SD rats were divided into three groups: control, operation control (OC) and test group. After 2/3 rat hepatectomy (partial hepatectomy, PH), three tissues (stomach, small intestine and liver) at different phases were taken out, then both 5-HT-IR endocrine cells and 5-HT-IR MCs in tissues were detected by immunohistochemical technique and MCs in tissues were identified by toluidine blue technique. In OC group, the protocols were the same, but liver was not resected. Results 1. Compared with the control, the amounts of 5-HT-IR endocrine cells in both stomach and small intestine in test and OC groups decreased 2 hours after PH (stomach P<0.05, intestinal P<0.01), but increased significantly at 6-72 hours (P<0.01) in test group. 5-HT-IR endocrine cells were not found in liver；2. Concerning the number of MCs in three tissues, there were no differnece between different phases and control except for reducing 48-96 hours after PH in liver in test group; 3.The amounts of 5-HT-IR MCs in stomach increased at 3.6 hours and 96 hours after PH(P<0.05), then increased significantly at 12-72 hours (P<0.01). The ones in small intestine increased at 2 hours and 120 hours after PH(P<0.05), then increased significantly at 3-96 hours (P<0.01). The ones in liver was decreased 48-72 hours after PH(P<0.05). In OC group, there were no differnece between different phases and control in three tissues. 4. 5-HT positive rate of MCs in stomach increased gradually 2.96 hours after PH, and one in small intestine did 0.5-120 hours (P<0.05). 5-HT positive rate in liver were increased slightly at 1.5-24hours, but decreased significantly 48-72 hours after PH. There was no differnece between OC group and control. Conclusion The amounts of both 5-HT-IR endocrine cells and 5-HT-IR MCs in gastrointestinal tract increased significantly during hepatocyte proliferation after PH, the data indicate these cells may provide 5-HT for liver regeneration.