Recent findings showed that the significance of CD163-positive macrophages in tumour progression. However, few studies related to the functions of CD163 in macrophages have been published. Therefore, we tried to uncover the involvement of CD163 in macrophage activation using CD163-deficient mice and human samples. At first we performed immunohistochemistry of CD163 using 45 samples of undifferentiated pleomorphic sarcoma (UPS). High density of CD163-positive macrophages was closely related to shortened progression free survival time and higher histological grade. Tumor development of sarcoma (MCA205 and LM8) cells were significantly abrogated in CD163-deficient mice as compared with WT mice. Co-culture study using peritoneal macrophages and MCA205 cells was performed, and we found that proliferation of MCA205 was significantly increased by co-culture with WT macrophages whereas this macrophage-induced proliferation of MCA205 was suppressed when CD163-deficient macrophages were used. IL-6 and CXCL2 production were found to be suppressed in CD163-deficient macrophages compared with WT macrophages. Silencing IL-6, but not CXCL2, abrogated the macrophage-induced proliferation of MCA205. By means of co-culture studies using human monocyte-derived macrophages and human sarcoma cell lines, similar macrophage-induced tumour cell proliferation was observed in TYLMS-1 and NMFH-1 cell lines, and notably silencing of CD163 abrogated the macrophage-induced tumour cell proliferation. Taken together, CD163 is related to protumour activation of macrophages and considered to be closely involved in tumour development and progression in murine and human malignant tumours. This work is collaboration with Dep. of Pathology, Kyushu University.