To clarify whether Irs2 is involved in impaired IL-4-induced M2a-subtype macrophage activation, we analyzed myeloid cell-specific Irs2-deficient (MIrs2KO) mice under the high-fat (HF) diet condition, and attempted to determine the signaling mechanisms by which IL-4/Irs2 pathway would regulate M2a-subtype macrophage activation. Here, IRS2 is linked to hydrops fetalis.