Podocyte injury is a hallmark of glomerular diseases, however, the intrinsic mechanisms are not elucidated. Previous studies have shown that B7-1 may be an inducer to podocyte injury. However, the intrinsic role of B7-1 in podocyte injury is controversial. In this study, we have identified that podocyte B7-1 definitely contributes to cell injury and glomerulosclerosis, and the underlying mechanisms are intimately correlated with activation of β-catenin pathway. Our studies provide the importance evidence to the role of B7-1 in podocyte injury and development of glomerulosclerosis.