Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle damage and weakness, accompanied by intramuscular fibrosis resulting from the loss of dystrophin. Despite recent breakthroughs in gene therapy, delaying muscle degeneration and reducing fibrosis remain major challenges in DMD patient care. Blood flow restriction (BFR) is a rehabilitation technique that involves temporarily reducing blood flow to a limb. It has been used increasingly in postoperative orthopedic patients to promote muscle regeneration and improve recovery. To investigate the effects of BFR on DMD muscles, we performed short-term (3 weeks) or long-term (3 months) BFR interventions in male D2-mdx mice. Mice in the BFR group underwent unilateral hindlimb BFR using a rubber band applied to the base of the right thigh for 10 minutes, followed by a 10-minute break, repeated for three cycles under general anesthesia with 1-2% isoflurane twice a week for three weeks or three months. Mice in the control (CTL) group underwent the same anesthesia procedure without BFR. After the 3-week BFR intervention, Evans Blue Dye staining revealed that the area of damaged muscle fibers in the gastrocnemius muscles was significantly reduced in the BFR group compared to the CTL group (CTL: 8.8 ± 5.1 % vs BFR: 0.5 ± 0.5 %, p= 0.041). After the 3-month BFR intervention, Masson-Trichrome staining revealed that the fibrotic area in the gastrocnemius muscles was significantly reduced in the BFR group compared to the CTL group (CTL: 26.8 ± 8.8 % vs BFR: 17.0 ± 2.5 %, p= 0.016). These results suggest that BFR improves myofiber integrity and reduces muscle injury and fibrosis in DMD muscle, highlighting its potential to prevent long-term muscle degeneration in DMD patients.