There is a growing body of research on the neural control of immunity and inflammation. However, it is not known if the nervous system can regulate the production of inflammatory myeloid cells from hematopoietic progenitor cells. Because the activation of the sympathetic nervous system in diabetic patients is well-documented and myeloid cells have been blamed for aggravating atherosclerosis, Dutta and colleagues used diabetic apolipoprotein E (ApoE)-deficient mice to investigate neural regulation of myelopoiesis. The diabetic mice had increased number and proliferation of splenic granulocyte macrophage progenitors (GMP), the immediate precursors of myeloid cells. Additionally, the spleens of diabetic mice and patients contained a higher number of tyrosine hydroxylase-expressing cells, indicating sympathetic hyperactivity. Surgical and chemical splenic sympathetic denervation in diabetic ApoE-/- mice diminished proliferation and differentiation of splenic GMP, resulting in decreased inflammatory myeloid cell numbers in the spleen and atherosclerotic plaques. This was accompanied by improved features of stable atherosclerotic plaques. Furthermore, Dutta and colleagues observed that splenic GMP of diabetic mice and patients expressed the 2 adrenergic receptor. Selective 2 blocker treatment in diabetic mice significantly reduced splenic GMP proliferation and myeloid cell production. Together, Dutta and colleagues’ study demonstrates that sympathetic activation instigates GMP proliferation and myeloid cell production in the spleen.