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AIM: To study the effects of estrogen on muscle damage and regeneration after acute passive gastrocnemius muscle strain injury in female Sprague-Dawley rats. METHODS: Rats were divided into 5 groups: ovariectomized,strained and treated with low-dosage estradiol (20 μg/d) (Elow), treated with high-dosage estradiol (200 μg/d) (Ehigh),treated with oil placebo (Oil), strained with no ovariectomy (Strain), and sham operated with no strain and no ovariectomy (Con). Muscle damage index [plasma creatine kinase (CK)], antioxidant indexes [glutathione (GSH),Vitamin E (Vit E), total antioxidant capability (TAC)], and muscle regeneration index (desmin) were investigated at7 d. RESULTS: The plasma CK activity increased but GSH, Vit E, and TAC levels decreased after muscle strain injury (Strain vs Con P<0.05). Plasma CK activity was the greatest while GSH, Vit E, and TAC were the lowest in the Oil group among the five groups (P<0.01). Plasma CK in the Ehigh and Strain groups was lower than that in the Elow group. Plasma GSH, Vit E, and TAC were higher in the Ehigh and Strain groups compared with the Elow group(P <0.05). The expression of desmin in the Ehigh and Strain groups was higher than that in the Elow group (P<0.01)while that in the Oil group was the lowest in all the five groups (P<0.01). CONCLUSION: Endogenous estrogen in normal female rats or exogenous estrogen in ovariectomized rats could improve antioxidant capability in vivo, so that reduced muscle damage and accelerated muscle regeneration post gastronemius muscle strain injury.