Macrophages, which belong to the immune system, are increasingly being recognized for their contribution to metabolic regulation. In two studies by Kang et al. (2008) and Odegaard et al. (2008) in this issue of Cell Metabolism, we learn that alternative activation (M2a) of resident macrophages in liver and adipose tissue depends highly on PPARdelta/beta activity, leading to improved fatty acid metabolism and insulin sensitivity.