OBJECTIVE: Several works highlight the role of CsA in the prevention of IRI, but none focus on isolated lungs. Our objective was to evaluate the effects of CsA on IRI on ex vivo reperfused pig lungs. METHODS: Thirty-two pairs of pig lungs were collected and stored for 30 minutes at 4 °C. The study was performed in four groups. First, a control group and then three groups receiving different concentrations of CsA (1, 10, and 30 μM) at two different times: once at the moment of lung procurement and another during the reperfusion procedure. The ex vivo lung preparation was set up using an extracorporeal perfusion circuit. Gas exchange parameters, pulmonary hemodynamics, and biological markers of lung injury were collected for the evaluation. RESULTS: CsA improved the PaO2 /FiO2 ratio, but it also increased PAP, Pcap, and pulmonary vascular resistances with dose-dependent effects. Lungs treated with high doses of CsA displayed higher capillary-alveolar permeability to proteins, lower AFC capacities, and elevated concentrations of pro-inflammatory cytokines. CONCLUSIONS: These data suggest a possible deleterious imbalance between the beneficial cell properties of CsA in IRI and its hemodynamic effects on microvascularization.