Cardiopulmonary bypass (CPB) stimulates systemic and pulmonary inflammation. Modified ultrafiltration (MUF) mitigates deleterious CPB effects by unclear mechanisms. We evaluated pulmonary inflammation in piglets undergoing CPB followed by MUF. Twenty-four piglets underwent 60 min of hypothermic CPB. MUF subjects (n=12) underwent hemoconcentration postCPB to the target hematocrit. Pulmonary vascular resistance (PVR), proinflammatory cytokine concentrations, and transpulmonary thromboxane gradients were determined at baseline, following CPB, and at end of the study (EOS) in MUF and control (n=12) groups. PVR significantly increased postCPB in both groups but decreased after MUF. MUF and control groups were similar in regards to systemic cytokine concentrations. Bronchoalveolar lavage concentrations of IL-6 and IL-8 significantly increased in controls throughout the study. Alveolar IL-6 and IL-8 were unchanged at EOS in MUF subjects, and IL-6 concentrations were significantly less than controls at EOS (P=0.015). Similarly, transpulmonary thromboxane gradient was significantly less at EOS in MUF subjects compared with controls (P=0.04). MUF removed circulating inflammatory mediators, lessened pulmonary hypertension, and reduced pulmonary-derived inflammatory markers, providing further evidence that MUF ameliorates pulmonary-based inflammation. These findings lend insight into mechanisms behind salutary clinical benefits of MUF after CPB.