A new two-photon fluorescent Cd(2+) probe APQ is developed by introducing a N(1),N(1)-dimethyl-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine binding group and a 4-methoxyphenylvinyl conjugation-enhancing group to the 2- and 6-positions of quinoline. This probe shows a large red shift and good emission enhancement under Cd(2+) binding. It also exhibits a high ion selectivity for Cd(2+) (especially over Zn(2+)) and a large two-photon absorption cross section at 710 nm. Two-photon microscopy imaging studies reveal that the new probe is non-toxic and cell-permeable and can be used to detect intracellular Cd(2+) under two-photon excitation.