This study investigate the effects of a 12-week barefoot walking exercise on female hormone, brain nerve growth factors and immunoglobulins in postmenopausal women. It aimed to provide the fundamental data for developing an effective exercise program to help postmenopausal women maintain a physically, psychologically, and socially healthy life in senescence. Postmenopausal women in C-city, Chungcheongbuk-do, were recruited and randomized between the barefoot walking group(n=11) and the shoes walking group(n=11) for subsequent analyses. The walking exercise program consisted of three 60-minute sessions per week for 12 weeks. The levels of estrogen, brain nerve growth factors and immunoglobulins were measured before and after the exercise. Two-way repeated measure ANOVA was performed to analyze the before-after difference between the barefoot walking group and the shoes walking group. The results acquired from this study are as follows. First, the estrogen levels during the 12-week walking exercise intervention were not influenced by the group or duration. However, the duration of the exercise significantly affected the barefoot walking group. Second, the brain nerve growth factors, namely, brain-derived neurotrophic factor(BDNF), insulin-like growth factor-I(IGF-I) and vascular endothelial growth factor(VEGF) were not significantly influenced by the group or duration during the 12-week exercise intervention. However, the barefoot and shoes groups significantly affected BDNF and VEGF. The duration of the exercise did not affect IGF-I in both groups. Third, IgG was significantly influenced by the group and duration during the 12-week exercise intervention. However, IgA and IgM were not significantly affected by the exercise group or duration. Exercise duration significantly affected the IgG of the shoes walking group and IgM of the barefoot walking group.