We demonstrated for the first time that (i) LPS induced the recruitment of Mo-DCs and secretion of inflammatory cytokines; (ii) the percentages of resident DCs, macrophages, and T cells significantly decreased in this mouse epididymitis model at 24 h; and (iii) knockout Myd88 on DCs prevented the release of inflammatory cytokines, which may be helpful for the treatment of epididymitis in the future. Here, MYD88 is linked to epididymitis.