Macrophage mannose receptor (MMR) is an important component of the innate immune system implicated in host defense against microbial infections such as candidiasis and in antigen presentation. We demonstrate here that the MMR expression is induced in mouse peritoneal macrophages following exposure to PPARγ ligands or to interleukine-13 (IL-13) via a PPARγ signaling pathway. Ligand activation of the PPARγ in macrophages promotes uptake, killing of Candida albicans, and reactive oxygen intermediates production triggered by the yeasts through MMR overexpression. We also show that MMR induction by IL-13 via PPARγ is dependent on phopholipase A2 activation and that IL-13 induces 15d-PGJ2 production and nuclear localization. These results reveal a novel signaling pathway controlling the MMR surface expression and suggest that endogenous PPARγ ligand produced by phospholipase A2 activation may be an important regulator of MMR expression by IL-13.