Rare earth elements (REEs) have undergone a steady spread in several industrial, agriculture and medical applications. With the aim of exploring a sensitive and reliable indicator of estimating exposure level to REEs, a simple, accurate and specific ICP-MS method for simultaneous direct quantification of 15 REEs (Y,La,Ce,Pr,Nd,Sm,Eu,Gd,Tb,Dy,Ho,Er,Tm,Yb andLu) in human urine has been developed and validated. The method showed good linearity for all REEs in human urine in the concentrations ranging from 0.001–1.000 μg • L with r > 0.997. The limits of detection and quantification for this method were in the range of 0.009–0.010 μg • L and 0.029–0.037 μg • L, the recoveries on spiked samples of the 15 REEs ranged from 93.3% to 103.0% and the relative percentage differences were less than 6.2% in duplicate samples, and the intra- and inter-day variations of the analysis were less than 1.28% and less than 0.85% for all REEs, respectively. The developed method was successfully applied to the determination of 15 REEs in 31 urine samples obtained from the control subjects and the workers engaged in work with manufacturing of ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggested that only the urinary levels of La (1.234 ± 0.626 μg • L), Ce (1.492 ± 0.995 μg • L), Nd (0.014 ± 0.009 μg • L) and Gd (0.023 ± 0.010 μg • L) among the exposed workers were significantly higher (p < 0.05) than the levels measured in the control subjects. From these, La and Ce were the primary components, and accounted for 88% of the total REEs. Lanthanum comprised 27% of the total REEs while Ce made up the majority of REE content at 61%. The remaining elements only made up 1% each, with the exception of Dy which was not detected. Comparison with the previously published data, the levels of urinary La and Ce in workers and the control subjects show a higher trend than previous reports.