Objective: To investigate the anti-inflammatory effect of the protein derived from the soluble factor of Heligmosomoides polygyrus(H. polygyrus) excretory-secretory in a colitis model.Methods: Colitis was induced by providing drinking water containing 3% dextran sodium sulfate(DSS) for a week. DSS was administrated in a cycle protocol, each cycle consisted of 7 days of 3% DSS in the drinking water and followed by 7 days of regular water. This study consisted of five treatment groups, including Groups A(control)received untreated water, B(DSS only, without excretory-secretory), and C–E injected(i.p.) with excretory-secretory protein(H. polygyrus excretory-secretory total, excretorysecretory 28 k Da and excretory-secretory 55 k Da, respectively). Mice received injection every week. The injection of excretory-secretory was started from the 6th weeks and continued until 11 weeks. At the end of 11 weeks of the experiment, mice were sacrificed,colon tissue was removed and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, real-time PCR and histology examination.Results: Mice received H. polygyrus excretory-secretory 55 k Da reduced mono-nuclear cell infiltrations. H. polygyrus excretory-secretory 55 k Da induced the down-regulation of m RNA interferong expression. There were significant differences in the expression of m RNA interferon in the colon of mice after the administration of the excretory-secretory55 k Da protein fraction compared with other groups(P < 0.001), whereas m RNA transforming growth factorb expression up regulated in the colon of mice after the administration of the excretory-secretory 55 k Da protein fraction compared with total excretory-secretory group(P < 0.05). The treatment of colitis in mice with excretorysecretory 55 k Da protein fractions modulated interleukin-10(IL-10) expression,whereas excretory-secretory total and excretory-secretory 28 k Da protein fractions insufficient promoted IL-10 expression. Excretory-secretory 55 k Da proteins fraction promoted IL-10 expression via Foxp3-independent pathways.Conclusions: Excretory-secretory 55 k Da protein could reduce inflammation and have potential therapy. H. polygyrus excretory-secretory 55 k Da was the soluble factor that may help in the development of novel treatments to cure colitis. Objective: To investigate the anti-inflammatory effect of the protein derived from the soluble factor of Heligmosomoides polygyrus (H. polygyrus) excretory-secretory in a colitis model. Methods: Colitis was induced by providing drinking water containing 3% dextran sodium sulfate (DSS DSS was administrated in a cycle protocol, each cycle consisted of 7 days of 3% DSS in the drinking water and followed by 7 days of regular water. This study consisted of five treatment groups, including Groups A (control) Received untreated water, B (DSS only, without excretory-secretory), and C-E injected (ip) with excretory-secretory protein (H. polygyrus excretory-secretory total, excretory secretory 28 k Da and excretory-secretory 55 k Da, Mice received injection every week. The injection of excretory-secretory was started from the 6th weeks and continued until 11 weeks. At the end of 11 weeks of the experiment, mice were sacrificed, colon tissue was removed and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, real-time PCR and histology examination. Results: Mice received H. polygyrus excretory-secretory 55 kDa reduced mono-nuclear cell infiltrations. H. polygyrus excretory-secretory 55 k Da induced the down-regulation of m RNA interferong expression. There were significant differences in the expression of m RNA interferon in the colon of mice after the administration of the excretory-secretory 55 k Da protein fraction compared with other groups (P <0.001) transforming growth factor b expression up regulated in the colon of mice after the administration of the excretory-secretory 55 k Da protein fraction compared with total excretory-secretory group (P <0.05). The treatment of colitis in mice with excretory secretory 55 k Da protein fractions model interleukin-10 (IL-10) expression, but excretory-secretory total and excretory-secretory 28 k Da protein fractions was promoted IL-10 expressio n.Excretory-secretory 55 k Da proteins fraction promoted IL-10 expression via Foxp3-independent pathways. Conclusions: Excretory-secretory 55 kDa protein could reduce inflammation and have potential therapy. H. polygyrus excretory-secretory 55 k Da was the soluble factor that may help in the development of novel treatments to cure colitis.