The aim of the present study was to determine the function of human amniotic epithelial cell transplantation (hAECT) in promoting the healing of rats with stage III pressure ulcer (PU) and to initially investigate its possible mechanisms. A total of 96 Sprague Dawley rats were allocated at random into the model, hAECT, conventional treatment or control groups (n=24 per group). In each group, 6 rats were observed to determine the wound-healing rate. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α in the wound tissue and serum were detected using reverse transcription-quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assay. The transplantation of hAECs significantly increased the healing rate of the stage III PUs and was accompanied by the significant upregulation of VEGF mRNA and protein expression levels and the significant downregulation of TNF-α mRNA and protein expression. Immunofluorescence staining showed that, on day 7 of transplantation, hAECs remained alive inside the skin tissues. Therefore, hAECT through subcutaneous injection appears to significantly improve the wound-healing rate of stage III PUs in rats, and this effect may be associated with the upregulation of the proangiogenic factor VEGF and the downregulation of the inflammatory cytokine TNF-α.