Adiponectin (APN) is an adipocyte-derived protein that regulates insulin sensitivity and displays anti-inflammatory activities in a variety of experimental models. The present study aimed at investigating the effect of APN deficiency on the inflammatory response to endotoxin (lipopolysaccharide, LPS) and Concanavalin A (ConA) in vivo in mice. Administration of a high dose of LPS (100 µg/mouse) induced production of comparable amounts of IL-6, TNF and IFN- in WT and APN KO mice. Furthermore, LPS-induced hypoglycemia, anorexia and body weight loss did not differ between WT and APN KO mice. Administration of a low dose of LPS (100 or 10 ng/g) in association with D-galactosamine induced equivalent mortality rates, hepatotoxicity and serum IL-6 in WT and APN KO mice. Finally, ConA-induced cytokine production and hepatotoxicity were not significantly different between WT and APN KO mice. These data indicate that-despite its well-described role as an anti-inflammatory molecule-endogenous APN does not play a critical role in modulating the inflammatory responses to LPS and ConA in mice.