Normal tissue damage following radiotherapy (RT) is still a major problem in cancer treatment. Therefore, the current work aimed at exploring the possible role of systemically injected bone marrow derived mesenchymal stem cells (BM-MSCs) and /or locally injected platelet rich plasma (PRP) in ameliorating the side effects of ionizing radiation on the rat's tongue. Materials & Methods: 12 rats served as control group (N) and 48 rats received a single radiation dose of 13 Gy to the head and neck region, then, they were equally divided into 4 experimental groups: Irradiated only group (C), Irradiated+MSCs group (S), Irradiated + platelet-rich plasma (PRP) group (P) and Combined group (PS). The animals in each group were divided into two blocks as animal sacrifice occurred in 3, 7 days after radiation. Then, tongues were dissected and examined histologically and for expression of bcl-2 by RT-PCR. Results: Histological examination of the treated groups (S), (P) and (PS) revealed an obvious improvement in the histological structure of the tongue; compared to the irradiated group (C); in addition to up regulated expression of bcl-2, indicating decreased apoptotic activity. Conclusion: BM-MSCs and PRP have shown positive effect in protection against the side effects of radiotherapy on normal oral mucosa, which was emphasized by decreasing apoptotic activity in these tissues. Nevertheless, combined use of both BM-MSCs and PRP did not reveal the assumed synergetic effect in oral tissue protection.