Objective: To investigate the mechanism by which cancer-associated fibroblasts (CAFs) promote macrophage M2 polarization through secretion of thrombospondin-2 (THBS2, TSP2). Methods: The expression and clinical significance of THBS2 in colorectal adenocarcinoma were analyzed using the TCGA database.The cellular origin of THBS2 was identified through the TISCH2 single-cell database combined with multiplex immunohistochemical staining, and its association with immune infiltration was assessed using TIMER2.0. Western blot, ELISA, and primary CAFs models were utilized to validate THBS2 secretion. qRT-PCR, Transwell assays, and PI3K/AKT pathway analysis were performed to systematically evaluate the regulatory effects of THBS2 on macrophage polarization, migration, and signaling. Results: THBS2 expression was significantly elevated in colon cancer tissues and closely correlated with advanced TNM stages and poor patient prognosis. Single-cell sequencing and experimental validation confirmed that THBS2 is specifically derived from CAFs and most strongly associated with M2 macrophage infiltration. Functional experiments demonstrated that CAFs-conditioned medium upregulated M2 markers (IL-10, CD206, ARG1) and enhanced macrophage migratory capacity. Recombinant TSP2 promotes p-PI3K/p-AKT phosphorylation levels in macrophages compared to the IL-4 group, augmenting M2 polarization. THBS2 knockdown significantly inhibited these pro-migratory and polarization effects. Conclusion: CAFs-derived THBS2 may drive macrophage M2 polarization and migration by activating the PI3K/AKT signaling pathway,thereby remodeling the colorectal cancer immune microenvironment and driving malignant progression. This study provides experimental evidence for immunotherapy strategies targeting the CAFs-THBS2 axis.