Objectives: Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. The aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. Methods: Approval for the research protocol was obtained from the local Board for Animal Experiments in accordance with Dutch laws and regulations (RU-DEC 2011-125). 14 male adult Sprague Dawley rats were used. The animals were divided into three groups: Group 1 (n = 4) and 2 (n = 2) to investigate the anatomy and histology of the soft palate respectively, and group 3 (n = 8) for surgical wounding of the soft palate. In the last group, the wound area was evaluated after 7 and 56 days using (immuno)histochemistry for muscle markers. Results: All animals survived surgery and showed no weight loss. After seven days, all wounds showed complete clinical healing. AZAN staining demonstrated an accumulation of collagen in the wound area, and extensive granulation tissue. Initial regeneration of muscle fibers and salivary glands was observed. Myofibroblasts were not present in the muscle tissue of the controls but only in blood vessels and salivary glands. In contrast, in the wound area in the experimental group showed large numbers of myofibroblasts was observed. Conclusions: We show that this model is suitable to study muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after surgery. Keywords: cleft palate, muscle regeneration, branchiomeric muscles, head mucles, satellite cells, tissue engineering