Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl3 for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl3 caused hippocampal apoptosis and impairment of spatial recognition memory of mice. CeCl3 effectively activated caspase-3 and -9, inhibited Bcl-2, and increased the levels of Bax and cytochrome c, promoted accumulation of reactive oxygen species in the mouse hippocampus. It implied that CeCl3-induced apoptosis in the mouse hippocampus could be triggered via mitochondrion-mediated pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012.