Exosomes play critical roles in colorectal cancer (CRC) in terms of oncogenesis, tumor cell survival, chemo-resistance, and metastasis. We have reported the proteome of exosomes released by human and mouse CRC cells. The proteins were predominantly focused on the translation regulation. We analyzed the exosomes of EMT CRC cell and epithelial-like CRC cell, and revealed that the upregulated proteins were predominantly enriched on the translation regulation. With a novel strategy, we traced the endpoint exosomally transported translation regulation proteins from CRC cells to macrophages and fibroblasts. Hence, we hypothesize that CRC cell derived exosomes regulate the globe translation of macrophage and fibroblasts, contributing to the formation of tumor microenvironment. We then employed our well-established model by using 3 CRC cell lines and macrophages to analyze the intracellular changes in terms of transcriptome and translatome, and characterized genome-wide translation regulation. The results showed that exosomes inhibited the translation process of fibroblasts due to the high ROS input from the tumor. We found that EMT CRC exosomes could up-regulate macrophage translation genome-wide, and promoted the transformation of macrophages to TAMs phenotype. we observed the preferential up-regulation of longer genes in macrophages treated with highly metastatic CRC exosomes, but not in those treated with Caco-2 exosomes. This study systematically researched the information flow of proteins from CRC cells to exosomes and then to target cells, and tempted to address the CRC cell exosomes educated macrophages in the systems biology view, which could lead to better understanding of translational control and its contribution to tumor microenvironment.