Introduction: Rib fractures, in particular serial fractures (3 or more fractured ribs ipsilateral) have serious consequences on the human body and quality of life and represent an important medical and socioeconomic problem. Aim: To determine the effects of pentadecapeptide BPC 157, L-arginin and L-NAME on healing of serial rib fracture in rats. Materials and methods: After intraperitoneal anesthesia, in male Winstar albino rats was performed the vertical transection of 8-10 ribs of right hemithorax at the lateral edge of the paravertebral muscles. The pentadecapeptide BPC 157 was administered intraperitoneal or orally.It was applied intraperitoneal (doses of 10 μg/kg and 10 ng/kg) immediately following a surgical procedure and then once daily and the last application 24 h before sacrifice. Orally (0.16 μg/ml and 0.16 ng/ml, a total of 12 ml/day) was applied in drinking water, from waking up to the animal sacrifice. In order to test the interaction with the NO system, L-NAME (5 mg/kg/day i.p.) and/or L-arginin (100 mg/kg/day i.p.) were administered alone or with BPC 157 to specific animal groups. The control groups were treated with 0.9% NaCl i.p. or with pure drinking water p.o. The daily clinical status of the animal (respiration frequency, chest movement) was observed, and on 20th day, during the first sacrifice interval, aortic blood was taken to analyze the acid-base status and the calcium and phosphate serum levels. At the same time, the local finding was verified in the sense of the formation of endothoracic fascia and scar, and then the right hemitorax was taken for further radiographic and histological analysis. After 60 days, the animals were sacrificed for biomechanical testing. Results: Animals treated with BPC 157 did not show pathological alterations in acid-base status. Calcium and phosphate serum levels were normal in all animal groups. BPC 157 alone or in combination with L-arginin and/or L-NAME leads to earlier healing of the rib fracture and increased creations of callus without scarring and adhesions at the place of fracture, as confirmed by radiographic and histological analysis. Biomechanical testing has shown that bone tissue of animals treated with BPC 157 on the site of fractures is stronger. Conclusion: The pentadecapeptide BPC 157 leads to earlier healing of fractured ribs and formation of stronger bones at the site of the fractures, and this is the effect of interacting with the NO system. The positive effect of pentadecapeptida BPC 157 is achieved regardless of the way of administration (oral or intraperitoneal) and the administered dose (10 μg or 10 ng).