Tumor-associated macrophages (TAMs) exhibit an immunosuppressive M2 phenotype and lead to failure of antitumor therapy. Infiltrated erythrocytes during hemorrhage have been recognized as a promising strategy for polarizing TAMs. However, novel materials that precisely induce tumor hemorrhage without affecting normal coagulation still face challenges. Here, tumor-targeting bacteria (flhDC VNP) are genetically constructed to realize precise tumor hemorrhage. flhDC VNP colonize the tumor and overexpress flagella during proliferation. The flagella promote the expression of TNF α , which induces local tumor hemorrhage. Infiltrated erythrocytes during the hemorrhage temporarily polarize macrophages to M1 subtype. In the presence of artesunate, this short-lived polarization is transformed into a sustained polarization because artesunate and heme form a complex which continuously produces reactive oxygen species (ROS). Therefore, the flagella of active tumor-targeting bacteria may open up new strategies for reprogramming TAMs and improving antitumor therapy. This article is protected by copyright. All rights reserved