Integrins are critical for migration and function of leukocytes in inflammation and autoimmune diseases. Integrin CD11b on DCs inhibits full T-cell activation and facilitates the development of peripheral tolerance by suppressing Th17 differentiation. We previously reported that CD11b highly expressed dendretic cells produced high IL-10 and CD11b negatively regulated TLRs-induced proinflammatory cytokines and type I interferon by promoting Syk-phosphorylated MyD88 and TRIF degradation via cbl-b. However relation of CD11b expression and IL-10 expression and whether CD11b functions in autoimmune diseases remain unclear. Here we found that CD11b deficient mice were more susceptible to DSS-induced colitis with decreased IL-10 production and Treg cells in vivo. CD11b-/- macrophages produced less TLR-induced IL-10, which resulting from decreased Src and Akt activation. Src and Akt inhibitor decreased while constitutively-active Src (CA-Src) and Akt (CA-Akt) increased TLRs-induced IL-10 production. Src inhibitor could not decreased IL-10 production in CA-Akt overexpressed macrophage, while Akt inhibitor could decrease IL-10 in CA-Src overexpressed macrophage, which indicates that Src functions upstream of Akt. We further found that Src interacted with and promoted degradation of inhibitory subunit p85 of PI3K. Our results indicate that CD11b maintains Treg number by promoting IL-10 production through Src-PI3K/Akt signal pathway.