Our previous epidemiological study revealed that co-exposure of [Cr(VI)] with small amount of heavy metals could induce peripheral blood element imbalance, but little was known about the contribution of Cr(VI) itself and the multi-element distribution profile in other target tissues. We explored element homeostasis in the blood, RBC, serum and lung after Cr(VI) exposure and Zn intervention. 60 Sprague-Dawley male rats received intratracheal instillation of Cr(VI) (0, 0.063, 0.630mgCr/kg) weekly and/or intragastric administration of zinc sulfate (0, 10mgZn/kg) daily for one month. Element contents and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were determined. Dose-response relationship was observed among rats exposed to Cr(VI). Ca, Mg, Mn in the blood, Fe, Mg, Se in the serum, and Mg and Zn in lung tissue decreased significantly, while Ca, Co, Cr, Mg, Mn, Se in RBC, and Ca, Co, Mo in the lung increased after Cr(VI) exposure. The alteration trends manifested differently, with RBC the most sensitive. Cr induced increase of urinary 8-OHdG, which decreased after Zn intervention. Zn intervention could help to restore element homeostasis after Cr(VI) exposure, especially for Ca, Fe, Mg and Se.