Mechanisms of particulate matter (PM)-induced cardiotoxicity are not fully understood. Direct translocation of PM-associated metals, including zinc, may mediate this effect. We hypothesized that following a single intratracheal instillation (IT), zinc directly translocates outside of the lungs, reaching the heart. To test this, we used high resolution magnetic sector field inductively coupled plasma mass spectrometry to measure levels of five stable isotopes of zinc ( 64 Zn, 66 Zn, 67 Zn, 68 Zn, 70 Zn), and copper in lungs, plasma, heart, liver, spleen, and kidney of male Wistar Kyoto rats (13 weeks old, 250–300 g), 1, 4, 24, and 48 h following a single IT or oral gavage of saline or 0.7 μmol/rat 70 Zn, using a solution enriched with 76.6% 70 Zn. Natural abundance of 70 Zn is 0.62%, making it an easily detectable tracer following exposure. In IT rats, lung 70 Zn was highest 1 h post IT and declined by 48 h. Liver endogenous zinc was increased 24 and 48 h post IT. 70 Zn was detected in all extrapulmonary organs, with levels higher following IT than following gavage. Heart 70 Zn was highest 48 h post IT. Liver, spleen and kidney 70 Zn peaked 4 h following gavage, and 24 h following IT. 70 Zn IT exposure elicited changes in copper homeostasis in all tissues. IT instilled 70 Zn translocates from lungs into systemic circulation. Route of exposure affects 70 Zn translocation kinetics. Our data suggests that following pulmonary exposure, zinc accumulation and subsequent changes in normal metal homeostasis in the heart and other organs could induce cardiovascular injury.