The aim of this study was to evaluate alterations in trunk adiposity (TA) over 9 months of resistance training (RT) and associate these changes with the hypertrophy of muscle mass (MM) in postmenopausal women (PW). The investigation used a sample that consisted of 22 PW (44-69 years old). The group was subjected to RT (60-80% of 1 repetition maximum) for the total body 3 d · wk(-1). Body composition (dual-energy x-ray absorptiometry) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone, E2 (Immulite system), and interleukin-6 (IL-6; enzyme-linked immunosorbent assay) were assessed at the beginning and end of the experiment. After RT, only women who acquired up to 5% TA gained MM, whereas women who acquired >5% TA exhibited increased IL-6 and no MM gain (p < 0.05). The ΔMM was negatively associated with time of menopause (r = -0.45, p < 0.05) and positively associated with baseline IGF-1 (r = 0.47, p < 0.05). Only ΔLE (leg extension) was negatively associated with baseline IL-6 (p < 0.05). Trunk adiposity growth (ΔTF, kilograms) was positively correlated with changes in IL-6 (r = 0.68, p < 0.05). The MM gain was negatively correlated with ΔTF (r = -0.63, p < 0.05) and changes in IL-6 (r = -0.73, p < 0.05). After adjusting all of the confounding variables, only baseline IGF-1 (positively) and changes in IL-6 (negatively) influenced MM, and only the increase in TA influenced IL-6. Our study suggests that increased levels of TA during RT increase IL-6 concentrations, which is a significant negative predictor of MM gain in PW.