Abstract: With the maturity of surgical techniques, the success rate of liver transplantation has been gradually increased. However, the establishment of long-term immune tolerance after operation still faces multiple challenges. Kupffer cells are tissue-resident macrophages, which could reside in the liver and polarize into different directions following liver transplantation, forming M1 Kupffer cells and M2 Kupffer cells. M1 Kupffer cells have pro-inflammatory function, whereas M2 Kupffer cells possess immunoregulatory function. It contributes to the establishment of immune tolerance by inhibiting the quantity and function of M1 Kupffer cells, or enhancing the quantity and function of M2 Kupffer cells. The polarization of Kupffer cells is regulated by many cytokines and signals, which provides an opportunity for therapies to establish immune tolerance of liver transplantation by interfering Kupffer polarization. In this article, the relationship between Kupffer cell polarization and immune tolerance of liver transplantation, and the mechanism of Kupffer cell polarization were reviewed, aiming to provide reference for establishing immune tolerance of liver transplantation.