Background and Objectives: The response of myostatin to resistance training with blood flow restriction is not perfectly clear. Therefore, the purpose of this study comparing the effects of eight weeks resistance training with blood flow restriction and traditional resistance training on myostatin, muscle mass and some related-muscle physiological factors in middle-aged women. Materials and Methods: In this clinical trial, 30 healthy and inactive middle-aged females (age: 45± 4 yr) were selected and randomly divided into three groups: control (C), blood flow restriction training (BFRT) and traditional resistance training (TST). Exercise training program was conducted for eight weeks and 3 days per week in 2017. Strength training for BFRT and TST performed with 20-30% one repetition maximum and 65-80% one repetition maximum, respectively. Before and after training program serum myostatin, muscular mass, muscular strength and muscular endurance were measured. For analyzing the data, paired t-test and one-way ANOVA were used. Results: There was observed a significant increase in muscular mass (p=0. 036), muscular strength (p=0. 001) and muscular endurance (p=0. 008) in the BFRT and TST groups in comparison with the C group. Myostatin had an insignificant dectease after two resistance trainings (p≥ 0. 05). Conclusion: It seems that low intensity strength training with blood flow restriction has similar effect with high intensity traditional strength training on muscular mass, strength and endurance in middle-aged women but does not have any effect on myostatin. So, low intensity resistance training with blood flow restriction may be a proper substitute for high intensity resistance training in middle-aged women.