Cutaneous radiation syndrome caused by high dose located irradiation is characterized by delayed symptoms, incomplete wound healing, and poor revascularization. Subcutaneous adipose tissue derived stromal/stem cells have been shown to improve skin repair in a minipig model of cutaneous radiation syndrome despite a subcutaneous defect being a consequence of radio-induced muscular fibrosis. Based on the pro-myogenic potential of stromal/stem cells, a new protocol combining subcutaneous and intramuscular injections was evaluated in a preliminary study. Six female minipigs were locally irradiated at the dose of 50 Gy using a Co source (0.6 Gy min) and randomly divided into two groups. Three animals received the vehicle (phosphate-buffer-saline solution) and three animals received three injections of 75 × 10 adipose tissue derived stromal/stem cells each time (day 25, 46, and 66 post-irradiation). Pigs were euthanized on day 76 post-irradiation before development of clinical skin symptoms. All minipigs exhibited a homogeneous skin evolution. Macroscopic observation of irradiated muscles showed prominent fibrosis and necrosis areas in controls as opposed to adipose tissue-derived stromal/stem cells injected animals. Moreover, muscle biopsy analysis highlighted a recruitment of myofibroblasts (Immune Reactive Score: p < 0.01), an interleukin 10 secretion and a muscle regeneration pathway activation after intramuscular injections of adipose tissue-derived stromal/stem cells (western-blot: respectively, 200-fold change difference and twofold higher in treated animals). Globally, these preliminary data suggest that intramuscular injections of adipose tissue-derived stromal/stem cells improve muscle regeneration in the cutaneous-radiation syndrome. Further work is ongoing to evaluate this therapeutic strategy on a larger animal number with a longer clinical follow-up.