Adiponectin, one of the adipokines secreted by adipocytes, possesses insulin sensitizing and anti-atherosclerotic properties. Tumor necrosis factor-alpha (TNF-alpha) is known to suppress the expression and secretion of adiponectin in adipocytes; however, the underlying mechanism remains poorly understood. Here, we demonstrate that GO6976 (a selective inhibitor of conventional protein kinase C (PKC)) prevents TNF-alpha-induced suppression of adiponectin secretion and expression in fully differentiated 3T3-L1 adipocytes, accompanied by attenuation of c-Jun N-terminal kinase (JNK) activation. Additionally, the transcriptional activity of peroxisome proliferator-activated receptor-gamma (PPARg) (a strong inducer of adiponectin) on the adiponectin promoter was inhibited in a PKC isoform-specific manner. These results raise the possibility that PKC is involved in TNF-alpha-induced suppression of adiponectin in 3T3-L1 adipocytes.