This study aimed to investigate the transportation and absorption mechanism of lanthanum carbonate [La-2(CO3)(3)] through the gastrointestinal (GI) tract using in vitro and in vivo models. The results demonstrated that La-2(CO3)(3) can be dissolved in gastric fluids and precipitated into lanthanum phosphate as the main transformed specie in intestinal fluid. Using Caco-2 cell monoculture and Caco-2/Raji B cell coculture models to simulate the intestinal epithelium and microfold (M) cells, it was found that the amount of lanthanum transported in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model (about 50 times higher), indicating that M cells play an important role in the intestinal absorption of La-2(CO3)(3). Furthermore, oral administration of La-2(CO3)(3) to Balb/c mice demonstrated that lanthanum can be absorbed by both Peyer's patches (PPs) and non-PPs intestinal epithelium, with a higher amount of absorption in the PPs per unit weight. This finding further confirmed that the lanthanum absorption in GI tract could be mainly due to the contribution of M cells. Meanwhile, the administration of La-2(CO3)(3) caused a marked lanthanum accumulation in liver, accompanied by the activation of Kupffer cells. This study clarified how La-2(CO3)(3) is absorbed through the GI tract to enter the body and would be helpful to evaluate its potential biological consequences of accumulation in human beings.