Introduction: This study was conducted to determine the effect of twelve weeks of aerobic training on serum levels of leptin, vaspin, total antioxidant capacity (TAC) and malondialdehyde (MDA) in obese middle-aged women. Materials and Methods: In this quasi-experimental study, 30 sedentary, middle-aged women (mean±SD age 48.30±3.02 yr, body mass index 30.89±3.23 kg/m2 and body fat 32.88 ±2.71%) were randomized into the experimental (n=15) and control (n=15) groups. The experimental group performed twelve weeks aerobic training (3 times per week at an intensity of 65-75 % of maximum heart rate reserve). Blood samples were collected 24h before and 48h after the training. Data was analyzed by Student's t-test (P< 0.05). Results: Results showed a significant decrease in serum levels of leptin and MDA (P values 0.009 and 0.01 respectively) while TAC significantly increased (P=0.01) in the experimental group. Body fat percentage significantly decreased in the experimental group (0.0001), but serum vaspin levels were not significantly different between the two groups (P=0.93). Conclusions: Regular aerobic training is associated with weight loss and reduced body fat in obese women. As leptin production occurs in adipose tissue, subsequent decrease in body fat percent, serum leptin levels also occurred. On the other hand, aerobic training can improve oxidation/anti-oxidation in the body by reducing MDA concentration and increasing TAC.