Breast cancer is a common tumor encountered in women, and triple-negative breast cancer (TNBC) has an extremely poor prognosis. The effect of leptin on the docetaxel sensitivity of MDA-MB-231 TNBC cells has not been investigated. The present study aimed to clarify the effect of leptin and M2 tumor-associated macrophages (TAMs) on the chemosensitivity of TNBC cell lines and its possible mechanisms. In the present study, the apoptosis of the MDA-MB-231 cell line was detected at 0, 24, 48 and 72 h using a Cell Counting Kit-8 assay to determine the appropriate concentration of docetaxel as well as the IC50 value. After determining the effect of leptin on TAMs, the conditioned medium with an appropriate concentration of docetaxel was collected to treat the breast cancer cells, and flow cytometry was used to detect the cell cycle distribution and apoptosis in different treatment groups. Interleukin 8 (IL-8) expression was detected using ELISA and western blot assay. The IL-8 antibody was used to neutralize IL-8, and invasion and scratch assays were used to detect changes in invasion and migration of breast cancer cells. Statistical analysis was performed using GraphPad Prism 9.0 and SPSS 22.0. It was revealed that the apoptotic rate of MDA-MB-231 cells in the leptin-treated TAMs group was lower than that in other groups. The expression of IL-8 was notably elevated in the group treated with leptin-activated TAMs compared with that in the other groups. The neutralization of IL-8 resulted in a significant reduction in the invasive migration of MDA-MB-231 cells compared with that in the non-neutralized group.