Since　its　first　description　in　1966,　macrophage　migration　inhibitory　factor　(MIF)　was　found　to　play　a　critical　role　in　inflammatory　and　immune　responses　as　well　as　in　disease　pathogenesis　especially　in　tumor　pathogenesis　and　cancer　progression.　MIF　is　expressed　in　different　cell　types　and　is　associated　with　many　disease　severity　and　tumor　pathogenesis.　Here,　we　investigated　the　influence　of　TLR7　and　TLR8　agonist　resiquimod　(R848),　an　immune　response　inducer　used　as　a　prophylactic　agent　for　several　infectious　diseases　as　well　as　anticancer　agents　and　vaccine　adjuvant　on　MIF　expression　in　cells　and　organs.　Humans,　mice　and　rats　cell　lines　from　different　tissues　(blood,　retinal,　nasopharynx,　brain　and　liver)　and　C57BL/6J　mice　organs　(brain,　liver　and　spleen)　were　used　for　this　investigation.　In　vitro,　R848　induced　MIF　gene　overexpression　except　in　brain　and　liver　cells.　Furthermore,　it　enhanced　cells　ability　to　release　soluble　MIF　and　differently　regulated　mRNA　expression　of　MIF-related　receptors　(CD74,　CXCR4,　CXCR2　and　CD44).　Its　influence　on　MIF　gene　expression　and　MIF　proteins　release　was　more　consistent　in　cancer　cells.　In　vivo,　a　strong　positive　expression　of　MIF　was　observed　in　different　regions　in　brain　and　spleen　in　response　to　R848　treatment;　however　in　liver,　increased　MIF　expression　was　observed　in　hepatocytes　only.　On　the　other　hand,　R848　treatment　had　induced　a　slight　enhancement　of　MIF　concentration　in　the　plasma　of　C57BL/6J　mice.　Taken　together,　these　data　suggest　that　R848　differently　regulates　MIF　mRNA　expression　depending　on　organ　types　and　could　influence　MIF　concentration　in　cellular　microenvironment.