Previously, we demonstrated that prostaglandin E2 (PGE2) induces C-C chemokine receptor type 7 (CCR7) expression on human monocytes, which stimulates their subsequent migration in response to the CCR7 natural ligands CCL19 and CCL21. In this study, we determined whether PGE2 affects CCR7 expression on macrophages. Flow cytometric analysis and chemotaxis assays were performed on Mono Mac-1-derived macrophage (MDMM-1) as well as unpolarized monocyte-derived macrophages (MDMs) to determine the CCR7 expression and functionality in the presence of PGE2. Data revealed that a MDMM-1 exhibited markedly downregulated CCR7 expression and functionality that were partially restored by treatment with PGE2. In MDMs, we observed a drastic downregulation of CCR7 expression and functionality that were unaffected following PGE2 treatment. Our data indicate that monocyte differentiation induces the loss of CCR7 expression and that PGE2 is unable to modulate CCR7 expression and functionality as shown previously in monocytes.