Connective tissue growth factor (CCN2) is a matricellular protein that is up-regulated in many fibrotic disorders and coexpressed with transforming growth factor ␤. CCN2 promotes fibrogenesis and survival in activated hepatic stellate cells, and injured or fibrotic liver contains up-regulated levels of CCN2 that are produced by a variety of different cell types, including hepatocytes. To investigate CCN2 action in vivo, transgenic FVB mice were created in which the human CCN2 gene was placed under the control of the albumin enhancer promoter to elevate hepatocyte CCN2 levels. Production of human CCN2 (hCCN2) messenger RNA and elevated CCN2 protein levels was demonstrated in transgenic livers, whereas levels of endogenous mouse CCN2 were comparable between transgenic and wild-type mice. Liver histology and liver function tests were unaffected in transgenic animals. However, after chronic administration of