Although many studies have addressed the effects of various physicochemical and biological factors on metal bioaccumulation in aquatic organisms, the influences of metal exposure history have drawn much less attention. In the present study, we investigated the effects of different Zn exposure regimes (concentration: 1–200 μg/L, duration: 1–7 d) on the subsequent biokinetics, metallothionien-like protein (MTLP) induction and subcellular distribution of Cd and Zn in Daphnia magna. Zn body burden increased significantly with elevated exposure concentrations, but was kept within a narrow range regardless of the 200-fold variation of Zn concentrations. Significant induction (7–14 folds) of MTLP by Zn exposure was evident, but was decoupled from the Zn body accumulation. Under different regimes of Zn exposure, Zn was evenly distributed in insoluble (cellular debris, intracellular organelles and metal-rich granules) and soluble fractions (heat sensitive protein and MTLP). However, >60% of Cd was bound with MTLP regardless of the exposure concentration and duration. The biokinetic processes including uptake from the dissolved phase, food assimilation and excretion of Cd and Zn were quantified with radioactive tracers. The uptake rate constants of Cd and Zn from the dissolved phase either remained comparable or increased following Zn pre-exposure, and the efflux of Zn increased by nearly two-fold to counteract the increased uptake from water. The dietary assimilation of Zn also decreased significantly in response to Zn exposure. However, Cd assimilation efficiency was kept relatively constant in each Zn pre-exposure regime. Our results showed that Zn exposure had significant influences on the biokinetics and physiology of daphnids. Daphnids attempted to maintain the Zn body burden within a narrow range by modification of biokinetic processes instead of subcellular distribution.