Background and Purpose: Diabetes Mellitus and its peripheral artery complications on could cause lower extremity muscle atrophy. Treatment of this condition mostly rely on exercise and surgical to preservation blood perfusion. Since low-level laser therapy has thought to be effective for both damaged vascular and muscle condition, the application of laser on muscle atrophy in peripheral artery disease with diabetes was tested. This study focus on: (1) examining whether laser treatment have effect the muscle preservation and vascular regeneration of type I diabetic-peripheral artery disease mice; and (2) evaluating the trend of relevance signal proteins to the regeneration process. Methods: 27 C57/BL6 were divided into 4 groups: control, laser, diabetes and diabetes-laser; diabetes mice were induced by intraperitoneal injection of streptozotocin, consequent by left femoral artery ligation. Animals then examined by laser Doppler for blood perfusion before treated with Al-GaInP-diode laser, 660 nm wavelength for 7 sessions, total 15 days. After sacrificed, muscles were collected, weighted, muscle tissue used for immunoflourescene for Collagen type IV, CD31, and protein extract were analyzed by western blot for AKT (protein kinase B), ERK (extracellular signal-regulated kinases), iNOS (inducible nitric oxide synthase), eNOS (endothelial nitric oxide synthase). Results: All diabetes mice was confirmed to have blood glucose above 200 mg/ dl, and blood perfusion of lower limb were impaired by femoral artery ligation. After LASER intervention, blood perfusion of diabetes group was significantly lower than diabetes laser group (p < 0.05), and muscle weight of diabetes group also have statistically decrease compare to control and laser groups (p < 0.05). Early protein assays showed no statistical differences among groups. Through immunofluorescence for Collagen type IV, the area of muscle fibers significantly decreased in diabetes group. Conclusion: The present results shows low laser therapy has positive effect on peripheral artery disease mice with diabetes, including increasing blood perfusion and preventing the muscle atrophy rate. Further analysis will be done to understand the underlying mechanism. Clinical Relevance: Approaching a promising noninvasive therapy for diabetic-peripheral artery disease complication.