Extracorporeal photopheresis has anti-inflammatory properties. The development of pulmonary fibrosis includes inflammatory episodes. This study evaluates effects of extracorporeal photopheresis in experimental pulmonary fibrosis. The bleomycin model of pulmonary fibrosis was used. Two groups of 4 rats received intratracheal bleomycin to induce fibrosis. The treatment group received infusions of photochemically treated leukocytes harvested from syngeneic animals. All animals were sacrificed at day 21 after fibrosis induction and analyzed with respect to lung histology and hydroxyproline content, cellular composition of bronchoalveolar lavages, serum and lavage concentrations of transforming growth factor-beta, interferon-gamma, and interleukin-10, and expression of selected genes in the lung. Interleukin-10 and transforming growth factor-beta protein concentrations increased in the plasma of treated animals, whereas the interferon-gamma protein concentration was higher in bronchoalveolar lavages. Interferon-gamma gene expression was up-regulated in the lung tissue of treated animals. No significant differences between treated and untreated animals were found with respect to hydroxyproline, histology, and lavage cell count. To conclude, extracorporeal photopheresis has positive molecular effects but does not attenuate experimental lung fibrosis with respect to histology, hydroxyproline, and lavage cell count in the applied treatment regimen. Further investigations of extracorporeal photopheresis in experimental pulmonary fibrosis are justified.