Abstract: Objective To investigate the regulatory mechanism of miR-27a/P-gp in blood exosomes of patients with triple-negative breast cancer (TNBC) before and after neoadjuvant chemotherapy (NACT). Methods Blood exosomes from TNBC patients in the NACT treatment group and the control group (epirubicin treatment alone) were isolated and identified. The expression of miR-27a/P-gp in blood exosomes was detected by RT-qPCR. The relationship between miR-27a and P-gp was investigated by luciferase reporter gene assay. Human microvessels endothelial cells (HMVECs) were treated with exosomes with low expression of miR-27a (the Exo-miR-27a - group), exosomes with high expression of miR-27a (the Exo-miR-27a + group), miR-27a mimics (the miR-27a-mimic group), negative control (the mimic-NC group) and plasmid with overexpression of P-gp (the pcDNA3.1-P-gp group).The level of VEGF was detected by ELSIA. The expression of VEGF-A was detected by Western blot. The angiogenesis was evaluated by tubule formation assay. Results Compared with the control group, the expression of miR-27a in blood and exosomes in the NACT group was down-regulated, while the expression of P-gp was up-regulated (P<0.05). Compared with those before NACT treatment, the expression of miR-27a in blood and exosomes was down-regulated after NACT treatment, while the expression of P-gp was up-regulated (P＜0.05). In HMVECs, the level of VEGF and angiogenesis increased in the Exo-miR-27a + group, compared with those in the Exo-miR-27a - group (P＜0.05). The level of VEGF and angiogenesis in the miR-27a-mimic group were higher than those in the mimic-NC group (P＜0.05). MiR-27a targeted P-gp inhibition. The level of VEGF and angiogenesis in the pcDNA3.1-P-gp group were lower than those in the pcDNA3.1-null group (P＜ 0.05). The level of VEGF and angiogenesis were lower in the pcDNA3.1-P-gp +miR-27a-mimic group than those in the pcDNA3.1-null +miR-27a-mimic group (P＜0.05). Conclusions Exosome miR-27a is down-regulated and P-gp up-regulated in TNBC patients after NACT treatment, and miR-27a promotes angiogenesis through inhibiting P-gp.