The aim of this study was to investigate the effects of 12 weeks of walking on plasma levels of leptin in postmenopausal women with breast cancer. Nineteen postmenopausal women with breast cancer (age: 55.05+2.7 years) who received surgery, chemotherapy and radiation-therapy and were receiving hormone therapy by letrozol were divided into two groups: control (N=8) and experimental (N=11). Subjects in the experimental group performed 12 weeks of an exercise program which consisted of 25 to 45 minutes of walking with an intensity of 45% - 65% of target heart rate, three times a week. In pretest and posttest, leptin, insulin, glucose, insulin resistance, anthropometric variables (body weight, BMI, WHR, and WC), body fat percentage and VO2peak were measured in both groups. Data were analyzed using ANCOVA (P<0.05). The results of this study showed that leptin, VO2peak, body weight and BMI had significant differences between experimental and control groups after 12 weeks (P<0.05). Leptin decreased 1.23% in the experimental group while it increased 7.4% in the control group. Body weight decreased 3.3% in the experimental group while it increased 2% in the control group. BMI decreased 2.3% in the experimental group while it increased 1% in the control group. VO2peak increased 8.2% in the experimental group while it decreased 5.5% in the control group. It can be concluded that walking can improve VO2peak, body weight, BMI and can decrease plasma levels of leptin in postmenopausal women with breast cancer.