: The occurrence and development of primary immune thrombocytopenia is closely related to autoimmune imbalanced. Thus, we conducted the current study to investigate the modulation of IL-35, a newly identified immunological self-tolerance factor on immune thrombocytopenic purpura (ITP). We were enrolled peripheral blood in 21 adult healthy volunteers, 21 active primary ITP patients and 16 ITP patients in remission. In the same period, bone marrow plasma was drawn from active primary ITP patients and 16 bone marrow donors. Enzyme-linked immunoassay was used to measure IL-35 levels in bone marrow mononuclear cells and peripheral blood mononuclear cells. Real-time quantitative PCR was used to study the mRNA expression levels of p35, Epstein-Barr virus-induced gene 3 in bone marrow mononuclear cells and peripheral blood mononuclear cells. Compared with the normal group, IL-35 levels of in ITP patients were decreased significantly. IL-35 level in bone marrow plasma was decreased more significantly than that in peripheral blood plasma at the same stage. The results showed that plasma IL-35 levels were significantly decreased in patients with active ITP compared with those of control individuals, and IL-35 levels in bone marrow plasma were decreased more significantly compared with those at the same stage. The pathogenesis of ITP is associated with decreased IL-35 levels. Further studies are needed to expand sample content and explore more in-depth investigate a possible role of IL-35 in the pathogenesis and course of ITP.