Galectin-3 is a pro-inflammatory biomarker associated with the pathogenesis of heart failure (HF). Physical-activity reduces the risk of heart-failure by modification of inflammation and fibrosis. The purpose of this study was to compare the effects of 8 weeks of high-intensity interval training (HIIT) versus moderate-intensity aerobic continuous training on a predictive factor of HF in postmenopausal women. Thirty sedentary postmenopausal women were randomly assigned to three groups. The first group performed the HIIT program at 60%-90%, and the second group performed an exercise program at 50%-65% of HR reserve. The control group maintained their normal daily regular physical activity level. The gene expressions of galectin-3 and lipid profiles were measured at the baseline and the end of Week 8. The HIIT and moderate-intensity aerobic continuous training attenuated the gene expression of galectin-3, serum low-density lipoprotein, cholesterol, and triglyceride concentrations and enhanced high-density lipoprotein concentrations. These changes were considerably higher in the HIIT group. Our results show that HIIT is superior to moderate-intensity aerobic continuous training in improving the decrease in HF risk in postmenopausal women.