PPARγ plays a key role in adipocyte specific gene expression. In this study, we assessed the effects of phorbol ester (TPA)‐sensitive PKC (c/nPKC) activation on the expression of adipocyte specific genes and inflammation related genes. Treatment with both TPA and TNFα decreased mRNA levels of PPARγ, aP2, LPL and adiponectin. TNFα, but not TPA, increased IL‐6 and MCP‐1 mRNA levels, Next, we investigated the effects of ligands which activate c/nPKC. Insulin and angiotensin II (AII), but not high glucose, reduced PPARγ, aP2 and adiponectin mRNA levels. AII‐induced suppression of these genes was restored in the presence of Go6976, a specific c/nPKC inhibitor, and candesartan, an AII receptor blocker. The effect of reduced insulin was prevented by Go6976 and LY294002, a specific PI 3‐kinase inhibitors. Our results indicate that activation of c/nPKC could debilitate and/or might deteriorate insulin sensitivity in vivo, through the reduction of PPARγ and adiponectin expression in adipocyte. © 2009 IUBMB IUBMB Life, 61(6): 644–650, 2009