Wnt/-catenin pathway plays an important role in embryonic liver development, morphogenesis and organogenesis. Here, we report the activation of -catenin during early postnatal liver growth. Modulation of -catenin expression was studied in CD-1 mice livers over a time course of 0 to 30 postnatal days (PD) and 3 months. An increase in total and active -catenin was observed in developing livers from PD 5 to 20. A concomitant increase in -catenin-TCF complex along with nuclear and cytoplasmic -catenin was also evident, which coincided with ongoing hepatocyte proliferation by PCNA immunohistochemistry. This activation of -catenin was multifactorial including cyclical inhibition of glycogen synthase kinase 3- (GSK3), suppression of casein kinase II- and transient increase in -catenin gene expression. Coprecipitation studies revealed formation of -catenin-cadherin complex at PD 5 whereas adequate -catenin-c-Met complex at the hepatocyte membrane did not form until PD 20, which might be contributing to the free -catenin pool during early postnatal growth. Furthermore, -catenin liver specific knockout mice exhibited smaller livers at PD 30, secondary to diminished hepatocyte proliferation. These data indicate that activation of -catenin is critical for early postnatal liver growth and development.