CD14 deficient (CD14^−/−) mice survived longer than wild-type (WT) C57BL/6J mice when inoculated with prions intracerebrally, accompanied by increased expression of anti-inflammatory cytokine IL-10 by microglia in the early stage of infection. To assess the immune regulatory effects of CD14 in detail, we compared the gene expression of pro- and anti-inflammatory cytokines in the brains of WT and CD14^−/− mice infected with the Chandler strain. Gene expression of the anti-inflammatory cytokine IL-13 in prion-infected CD14^−/− mice was temporarily upregulated at 75 dpi, whereas IL-13 gene expression was not upregulated in prion-infected WT mice. Immunofluorescence staining showed that IL-13 was mainly expressed in neurons of the thalamus at 75 dpi. These results suggest that CD14 can suppress IL-13 expression in neurons during the early stage of prion infection.