Hyposalivation is an intractable side‑effect of radiotherapy for head and neck cancer. It is caused by the irreversible loss of acinar cells and decreased saliva secretion. However, this situation severely compromises the quality of life of affected patients. Currently, there is no effective treatment for this condition. In the present study, we developed a novel approach to regenerate the function of the irradiation‑damaged salivary glands using human adipose tissue‑derived stem cell (hADSC) intraglandular transplantation. ZsGreen‑labeled hADSCs were adoptively transferred into Sprague‑Dawley (SD) rat submandibular glands immediately following exposure to 18 Gy irradiation. A higher salivary flow rate (SFR) was observed in the hADSC‑treated group. Tissue improvement, including angiogenesis, anti‑apoptosis and anti‑fibrosis, was detected in the hADSC‑treated glands as compared to the untreated glands. Quantitative reverse transcription PCR (RT-qPCR) revealed a significantly higher expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), cyclooxygenase‑2 (COX‑2) and matrix metalloproteinase‑2 (MMP‑2) in the hADSC‑treated rats. Furthermore, immunohistochemical analysis indicated that the hADSCs had differentiated into acinar and ductal cells in the rat submandibular glands. Thus, our results suggest that hADSCs are able to regenerate irradiation‑damaged salivary glands through glandular transplantation.