Bcr is a serine/threonine kinase activated by platelet-derived growth factor that is highly expressed in the neointima after vascular injury. Here, we demonstrate that Bcr is an important mediator of angiotensin (Ang) II and platelet-derived growth factor–mediated inflammatory responses in vascular smooth muscle cells (VSMCs). Among transcription factors that might regulate Ang II–mediated inflammatory responses we found that ligand-mediated peroxisome proliferator-activated receptor (PPAR) transcriptional activity was significantly decreased by Ang II. Ang II increased Bcr expression and kinase activity. Overexpression of Bcr significantly inhibited PPAR activity. In contrast, knockdown of Bcr using Bcr small interfering RNA and a dominant-negative form of Bcr (DN-Bcr) reversed Ang II–mediated inhibition of PPAR activity significantly, suggesting the critical role of Bcr in Ang II–mediated inhibition of PPAR activity. Point-mutation and in vitro kinase analyses showed that PPAR was phosphorylated by Bcr at serine 82. Overexpression of wild-type Bcr kinase did not inhibit ligand-mediated PPAR1 S82A mutant transcriptional activity, indicating that Bcr regulates PPAR activity via S82 phosphorylation. DN-Bcr and Bcr small interfering RNA inhibited Ang II–mediated nuclear factor B activation in VSMCs. DN-PPAR reversed DN-Bcr–mediated inhibition of nuclear factor B activation, suggesting that PPAR is downstream from Bcr. Intimal proliferation in low-flow carotid arteries was decreased in Bcr knockout mice compared with wild-type mice, suggesting the critical role of Bcr kinase in VSMC proliferation in vivo, at least in part, via regulating PPAR/nuclear factor B transcriptional activity.