In the present study, after the SSP treatment of colitis mice with SKYD syndromes for 7 days, TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins were inhibited, and IκB was activated in colonic mucosal tissues, which suggested that the therapeutic effect of SSP on experimental colitis is closely related to the TLR4/NF-κB signaling pathway. This evidence concerns the gene MYD88 and colitis.