Background: Age-related changes of salivary glands affect their functions and structure. Rab3D is localized to zymogen granules (ZGs) and plays a critical role in secretory granules maturation and exocytosis. Nowadays, application of life sciences is used in tissue regeneration. Objective: The current study was designed to explore the possible effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on the function and morphology of ZGs in parotid glands of senile rats.Design: Fourteen clinically healthy male albino rats were used. Seven adult rats aged 6-8months were named as Control adult (Group I). The remaining seven rats aged 18-20 months (old age). For each old age rat the parotid gland of the left side represented the Old age untreated (Group II) and injected by 0.2 ml phosphate buffered saline (PBS). While, the parotid gland of the right side represented the Old age treated by stem cells (Group III) and injected by 1-1.5 x 106 BM-MSCs in 0.2 ml PBS. At the end of the experimental period (after four weeks), all the rats were euthanized and the parotid salivary glands were dissected out. The sections were prepared for histological, immunohistochemical and ultra-structural examinations in addition to real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Statistical analysis: Data obtained from histomorphometric analysis and qRT-PCR assay were statistically described in terms of mean ± standard deviation (± SD).Results: Histological examination of Group I showed normal histological features of the terminal secretory units. Group II revealed that most of the acini were distorted and showed fatty degeneration. The oncocytes were noticeable. Group III illustrated more or less normal histological features. Immuno-expression of Rab3D was strong in Group I and Group III but mild in Group II. The ultra-structural examination of Group I showed apparently large and spherical ZGs. Group II revealed apparently small and ellipsoid ZGs. Lamellated lipofuscin granules were observed. Group III demonstrated obviously large and well defined spherical ZGs. The statistical results revealed that the highest means of Rab3D immunoreactivity area % and relative Rab3D gene expression level were demonstrated in Group I, followed by Group III, and the least values were for Group II. Conclusions: Allogeneic BM-MSCs have positive effect on age-related changes of parotid salivary glands by restoring the terminal secretory units’ structure, Rab3D expression as well as ZGs structure and function.