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Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP‐2) seems to cleave vasoactive peptides. This study examined whether MMP‐2 and MMP‐9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin‐1 or with reductions in circulating adrenomedullin and calcitonin gene‐related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 μg/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 μg/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole‐blood lead levels (9 …