Purpose: the objective of the present study was to evaluate the effect of BM-MSCs on irradiated submandibular salivary glands in mice and to determine at which stage post-irradiation the cells should be transplanted. Materials and methods: 58 adult male mice were used, 10 for preparation of PKH-26-labeled BM-MSCs and the remaining 48 mice were divided into: control group (GӀ) consisted of 6 mice without radiation and experimental groups consisted of 42 irradiated mice irradiated with a single dose of 15Gy. They were randomly divided into three groups: GӀӀ (+ve control): 18 irradiated not treated mice and two treated groups each consisted of 12 irradiated mice and treated with intraglandular injection of labeled BM-MSCs, 24 hours (GӀӀӀ) and at day 11 (GΙV) post-radiation. Animals were sacrificed at day 6, day 30 and day 90 post-radiation. The submandibular glands were collected, one gland was routinely processed for histological examination using H&E staining and the other was prepared for immunohistochemical study using immunofluorescence staining with anti- α-amylase 1 antibody. Results: BM-MSCs produced marked improvement in salivary gland tissue architecture, histology of parenchymatous and stromal structures and glands function indicated by marked increase in α amylase 1 production compared with +ve control group, with GӀӀӀ showed greater improvement than GΙV. Conclusions: It could be concluded that: intraglandular transplantation of BM-MSCs could successfully regenerate radiation-induced submandibular salivary gland damage and restore the gland function. The early transplantation of BM-MSCs 24 hours post-radiation was markedly more beneficial than the transplantation at day 11 post-radiation.