We recently demonstrated that preadipocytes exhibit functional features of macrophages, such as phagocytosis and anti‐microbial activity, suggesting that preadipose cells could play a role in the inflammatory process or immune response. The aim of this study was to compare these functions of both macrophages and cells from stroma‐vascular fraction (SVF) of the adipose tissue in two different situations, obesity and inflammation, characterized by alterations in immune responsiveness. We demonstrated that ob/ob mice exhibited strong decrease in antimicrobial activity of both macrophages and SVF. This defect is compensated in SVF, at least in part, by an enhancement of phagocytosis that does not seem to be due to an increased macrophage number. In vitro leptin treatment of SVF and macrophages from obese mice did not restore their immune defects. Thioglycollate treatment of lean and obese mice induced an inflammatory process that led to an increase in macrophage activity in both strains. This stimulation also observed in SVF from lean mice is not present in obese ones. This work demonstrated that SVF immune functions could be modified in different pathological situations such as inflammation and obesity and sustained the new physiological role of preadipocytes in these processes. © 2001 Wiley‐Liss, Inc.