Annexin A1 (AnxA1), a Ca2+ and phospholipid binding protein, is a mediator of glucocorticoid (GC) action in the neuroendocrine and host defence systems. It acts at least in part via members of the membrane bound formyl peptide receptor (Fpr) family, particularly Fpr2 which is also a target for the anti-inflammatory eicosanoid, lipoxin A4, as well as pro-inflammatory bacterial formylated peptides. Unregulated inflammation underlies many diseases, including sepsis. Our recent studies have revealed tissue specific roles for the AnxA1-Fpr2 system in the resolution of inflammation in the brain, pituitary gland and adrenal cortex in an animal model of sepsis. They also revealed that this system plays a pivotal role in mediating the profound impairment of adrenocortical function which follows the initial hypersecretion of GCs in this model. These and other data provide further evidence of the complex interplay between endogenous mediators and bacterial peptides in the manifestation and resolution of inflammation.