Prostaglandin D2 and its derivatives PGJ2 and Δ12-PGJ2 strongly stimulate the synthesis and secretion by white adipocytes of the neurotrophin NGF. Here we have explored whether PGD2 and the J2-series prostaglandins have pervasive effects on adipokine production. The influence of these prostaglandins on the production of the adipocyte hormones leptin and adiponectin, and the inflammatory factors IL-6 and monocyte chemoattractant protein 1 (MCP-1), were examined in 3T3-L1 adipocytes. PGD2 induced a reduction in adiponectin and leptin mRNA, and the secretion of these adipokines was also inhibited, the effect being greater with leptin (up to 10-fold) than with adiponectin (twofold). In contrast, PGD2 induced a marked stimulation of IL-6 and MCP-1 expression; with IL-6, this was rapid, the mRNA level increasing by >50-fold by 1 h. The rise in mRNA was accompanied by an increase in IL-6 and MCP-1 release (up to 100- and 6.5-fold, respectively). The effects of PGD2 were generally mirrored by PGJ2 and Δ12-PGJ2; Δ12-PGJ2 was a particularly strong stimulator of IL-6 production. These results indicate that PGD2 and the J2-series prostaglandins PGJ2 and Δ12-PGJ2 can have major effects on the synthesis and release of key adipokines. Such effects could be important in the inflammatory response in adipose tissue.