Purpose <p>Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by damage to the epithelial barrier and intestinal inflammation; there is currently no standard treatment. Recent evidence suggests that worms and their by-products may have potential to treat IBD, owing to their immunomodulatory effects in humans. We investigated the effects of the recombinant <i>Echinococcus granulosus</i> antigen EgM123 on host immunity and inflammation.</p> Methods <p>We produced recombinant EgM123 to test its effects in the dextran sodium sulfate (DSS)-induced colitis mouse model. Mice were immunized with EgM123 three times via intraperitoneal injection and then challenged with 4% DSS in the drinking water for 1 week; they were observed daily for weight, mobility, and stool. After necropsy, fixed tissues/organs were sectioned and stained with hematoxylin and eosin to assess inflammation. Cytokine levels were detected by ELISA and reverse transcription polymerase chain reaction. Colitis severity was assessed by colon length, weight loss, and a semi-quantitative score of morphological changes.</p> Results <p>EgM123 had protective effects against colitis in mice. Histopathological analysis of the colon revealed a significant reduction in intestinal inflammation caused by DSS, which was associated with downregulation of the Th1/Th17 response in the colon. Administration of EgM123 before colitis induction limited the severity of intestinal inflammation and the disease index score, inhibited TNF-α secretion, and induced IL-10 expression.</p> Conclusions <p>EgM123 may alleviate colitis by inhibiting the Th1 response and inducing Th2 immunity. Immunotherapy with EgM123 may represent a strategy to modulate the inflammatory processes involved in IBD.</p>