Abstract Trichinella spiralis (T. spiralis) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement in spleen impairment and inflammation in the early infection of T. spiralis has yet to be fully elucidated. This study analysed histological, inflammation, and macrophage polarisation of the early T. spiralis-infected mice treated with TJ-M2010-5. MyD88 promoter methylation results showed that the methylation levels in the 5 d group were lower compared to the control group (P