We have recently identified apelin as a novel adipokine up‐regulated by insulin and obesity. Since obesity and insulin resistance are associated with chronically elevated levels of both insulin and TNFα, the present study was performed to investigate a putative regulation of apelin expression in adipocytes by TNFα. Herein, we report a tight correlation between apelin and TNFα expression in adipose tissue of lean and obese humans. Apelin regulation by TNFα was further studied in cultured explants of human adipose tissue. The endogenous expression of TNFα in adipocytes isolated from the explants was accompanied by a 6–9 h subsequent increase of apelin expression in adipocytes. This increase was reversed by inhibiting TNFα expression with 100 µM isobutylmethylxanthine. In different mouse models of obesity, expression of both TNFα and apelin was also significantly increased in adipocytes of obese mice. Furthermore, short‐term exposure to an i.p. injection of TNFα in C57Bl6/J mice induced an increase of apelin expression in adipose tissue as well as apelin plasma levels. Finally, a direct positive effect of TNFα has been shown in differentiated 3T3F442A adipocytes on apelin expression and secretion. The signaling pathways of TNFα for the induction of apelin were dependent of PI3‐kinase, c‐Jun NH2‐terminal kinase (JNK), and MAPK but not PKC activation. All together, these findings suggest that apelin might be a candidate to better understand potential links between obesity and associated disorders such as inflammation and insulin resistance.—Daviaud, D., Boucher, J., Gesta, S., Dray, C., Guigne, C., Quil‐liot, D., Ayav, A., Ziegler, O., Carpene, C., Saulnier‐Blache, J.‐S., Valet, P., Castan‐Laurell, I. TNFα up‐regulates apelin expression in human and mouse adipose tissue. FASEB J. 20, E796–E802 (2006)