Osteopontin (OPN) produced by alveolar macrophages functions as a fibrogenic cytokine in the development of bleomycin (BLM)-induced murine pulmonary fibrosis, and OPN mRNA is expressed on lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The present study investigates plasma OPN levels in human interstitial pneumonia (IP) and their relationships with disease severity by analyzing the correlation between plasma OPN concentrations and pulmonary functions. The concentrations of OPN in plasma were measured in 17 patients with IP, in 9 with sarcoidosis and in 20 healthy controls using an antigen-capture enzyme-linked immunosorbent assay. The concentrations of OPN in plasma were significantly higher in IP patients than in those with sarcoidosis or in controls. Based on a Receiver Operating Characteristic curve analysis, cut-off points between 300 and 380 ng/ml discriminated between IP and control subjects with 100% sensitivity and 100% specificity. In such case, the sensitivity for sarcoidosis decreased (55.5-33.3%) in cut-offs with 100% specificity. Plasma OPN levels inversely and closely correlated with arterial oxygen tension (PaO2) in patients with IP. Immunohistochemically, OPN was localized predominantly in macrophages and airway epithelium. These findings suggest that plasma OPN levels were found to be associated with the presence of IP, and that OPN play an important role in the development of IP.