Background: Maxillofacial bone engineering showed promising result; however, its healing mechanisms and effectiveness had not been fully understood. Objectives: The study compared the bone healing mechanism and osteogenic capacity between bovine bone mineral (BBM) scaffold loaded with human amniotic membrane stem cell (hAMSC) and autogenous bone graft (ABG) in the reconstruction of critical size mandibular defect. Methods: Critical size defects were made at mandible of 45 New Zealand White rabbits which were subsequently reconstructed with BBM-hAMSC, BBM alone, and ABG, respectively. At the end of first, second, and twelfth weeks, five rabbits from each group were sacrificed for histology and immunohistochemistry staining. Expressions of vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), Runt-related transcription factor 2 (Runx2) and angiogenesis were analysed in first and second week, while Runx2, osteocalcin, collagen-I fibres, trabecular area and bone incorporation were analysed in twelfth week. Findings: Expressions of VEGF, BMP-2, Runx2 and angiogenesis were higher in ABG compared with BBM-hAMSC group in the first and second week group. In twelfth week expressions of Runx2 and osteocalcin as well as thickness of collagen-I fibres were significantly higher in BBM-hAMSC compared to ABG group, while there was no statistically difference in trabecular area and bone incorporation between BBMhAMSC and ABG group. Conclusion: Early healing activities were higher in ABG than in BBM-hAMSC, while osteogenic activities in the late stage of healing were higher in BBM-hAMSC compared to ABG. In addition, the osteogenic capacity of BBM-hAMSC was comparable to ABG in the reconstruction of critical size defect in the mandible.