Background and objectives: Sentinel lymph node biopsy is important for metastasis surveillance in the management of a number of human cancers. Identification of sentinel lymph nodes may be facilitated by the use of several methods including methylene blue injection. However tissue necrosis is a known effect of methylene blue application. This study aimed to investigate the effects of methylene blue injection on skin flaps using a rodent model. Methods: Modified McFarlane flaps were prepared using Wistar Albino rats. Local injection of methylene blue was given to one group while saline was injected into the control group. A third group received systemic methylene blue via intraperitoneal injection. Observational and histological comparison was made between the groups to investigate the necrotic effects of methylene blue on skip flaps. Results: The control group's surviving flap areas were significantly larger than local methylene blue group's surviving flap area. However, there was no significant difference in skin flap survival area between the control group and the systemic methylene blue group. Furthermore, there is no significant difference between local and systemic methylene blue group's surviving flap areas. Conclusions: Local methylene blue injection increases skin necrosis and decreases rates of surviving flap areas in an experimental rat models.