Ischemic reperfusion injury is important problem in vascular, traumatology orthopedic, related to extremity rescue after ischemic period. Mortality is 20% in amputation and about 30 – 40% cause death in intensive care unit. The use of herbal medicine is increasingly popular, with the addition of soursop leaf extract (Annona Muricata) which has antioxidant properties that are useful for reducing oxidative stress caused by ischemic reperfusion injury, seen through increased levels of Glutathione (GSH) and decreased levels of Malondialdehyde (MDA). To determine the effect of soursop leaf extract in preventing ischemic reperfusion injury in skeletal muscle of white rats after using a tourniquet by increasing levels of Glutathione (GSH) and decreasing levels of Malondialdehyde (MDA). Ischemia of the hind legs of rats was induced for 4 hours by administering a tourniquet on the hind legs of rats, followed by reperfusion for 1 hour. Rats were euthanized. The gastrocnemeus muscle was removed after reperfusion. Gastrocnemeus muscle injury was evaluated in 4 groups: 1. Control (saline), 2. Soursop leaf extract 200mg/kgbw, 4. Soursop leaf extract 400mg/kgbb. 4. Control Without Treatment. The group with soursop leaf extract significantly reduced muscle tissue MDA levels compared to the control group (p<0.05). The higher the levels of soursop leaf extract will significantly reduce the tissue MDA levels. The group given soursop leaf extract significantly increased tissue GSH levels compared to the control group (p<0.05). The higher levels of soursop leaf extract will increase tissue GSH levels significantly. Giving soursop leaf extract (Annona Muricata) can reduce MDA levels and increase GSH, as well as reduce oxidative stress in ischemic reperfusion injury of skeletal muscle which indicates that soursop leaf extract has a protective effect against free radicals in preventing ischemic reperfusion injury.