<p>Non-small-cell lung cancer (NSCLC) is amongst the most common tumors, which is responsible for most cancer-related mortality worldwide. Tumor-associated macrophages (TAMs) can regulate tumor microenvironment (TME) and malignant progression of NSCLC; however, the regulatory mechanisms of TAMs exosome (M2-Exo) in the context of NSCLC progression are still unclear. In this study, exosomes isolated from TAMs (M2-Exo) were subjected to FISH and RT-qPCR to explore hsa_circ_0000896 expressions in NSCLC specimens. Dual-luciferase reporter data were utilized to investigate hsa_circ_0000896 downstream targets. Transwell migration, 5-ethynyl-2′-deoxyuridine incorporation, cell counting, and wound hearing experiments were performed to assess NSCLC cell migration and proliferation. Hippocampus experiment was used to detect cellular metabolism. Mouse tumor xenograft model was constructed to assess the hsa_circ_0000896 roles in NSCLC metastasis and progressions. The data revealed that M2-Exo treatment promoted NSCLC cell proliferation and migrations. Hsa_circ_0000896 in M2-Exos mediated NSCLC malignant progression, which was ameliorated by downregulation of hsa_circ_0000896 expression. Both SLC2A3 and miR-503-5p were identified as hsa_circ_0000896 downstream targets. SLC2A3 overexpression or miR-503-5p suppression can reverse hsa_circ_0000896 silence inhibit effects to NSCLC malignant progression. The hippocampus experiment confirmed that downregulation of hsa_circ_0000896 inhibited aerobic glycolysis by regulating miR-503-5p/SLC2A3. A549-DDP were used to construct a subcutaneous tumor model, outcomes of which showed that downregulation of hsa_circ_0000896 increased NSCLC chemosensitivity. Together, our results revealed that exosomes from TAMs promoted glycolysis and malignant progression of NSCLC by delivering hsa_circ_0000896. And hsa_circ_0000896 can promote glycolysis by regulation miR-503-5p/SLC2A3.</p>