The 110 kDa trans-membrane glycoprotein CD68 is highly expressed by human monocytes and tissue macrophages. However, in addition to the monocyte/macrophage system, CD68 has been also found in normal and tumor cells with no macrophagic activity such as lymphocytes, fibroblasts, endothelial cells, small intestinal epithelial cells, and neoplastic cells of different origins. Here, for the first time we demonstrate the immunohistochemical localization of CD68 in the principal cells of the cranial and caudal segments of rat epididymis. These results were confirmed by biochemical analyses showing the expression of CD68 mRNA transcripts and the protein in the epididymis tissues. Our findings, while providing further evidence that CD68 expression is not restricted to the monocyte/macrophage system, suggest that the glycoprotein might be involved in the functions of epididymal principal cells that contribute to spermatozoa maturation process.