Plasminogen, the precursor of plasmin, is a serine protease that plays a fundamental role in the intravascular thrombolysis. For the first time, by using high-resolution mass spectrometry, data on the oxidative modifications of the plasminogen molecule under induced oxidation were obtained. The FTIR data show that, under oxidation on the protein, its secondary structure also undergoes the rearrangements. The high tolerance of plasminogen to oxidation can be due to both the closed conformation and the ability of some Met residues to serve as ROS trap.