Wilson disease is an inherited autosomal recessive disorder causing copper accumulation and consequent toxicity. D-Penicillamine, a potent metal chelator, is an important therapy for Wilson disease. To investigate the changes of metal elements under the treatment of D-penicillamine, we determined the levels of Cu, Zn, Mg, Ca, Fe, Se, Mn, Pb, Hg, Cd, As, Tl, and Al by ICP-MS in 24-h urine of 115 Wilson disease patients who had received treatment with D: -penicillamine for 1 month to 22 years at maintenance doses, as well as 115 age-matched, healthy controls. The levels of Cu, Mg, Ca, Zn, Hg, Pb, Tl, Cd, and Mn in the 24-h urine of the cases were significantly higher than those of the controls (P < 0.05), and the observed increases in the levels of Mg, Ca, and Zn were directly correlated with the treatment duration with Pearson Correlation Coefficient (R) of 0.356 (Mg), 0.329 (Ca), and 0.313 (Zn), respectively (P < 0.05). On the other hand, the levels of Al and As in the 24-h urine were lower than those of the controls (P < 0.05) and were negatively correlated with the treatment time with R of -0.337 (Al) and -0.398 (As), respectively, (P < 0.05). Thus, this study indicates that the levels of metal elements may be altered in patients with Wilson disease under the treatment of D-penicillamine.