BACKGROUND Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by inhalation of numerous antigens. Pathologically, chronic HP tends to show usual interstitial pneumonia (UIP) and fibrotic nonspecific interstitial pneumonia (fNSIP) patterns. Patients with UIP pattern present insidious onset and a risk for acute exacerbations. METHODS To evaluate the proteomic differences of bronchoalveolar lavage fluid (BALF) between UIP and fNSIP patterns, BALF from seven patients with UIP pattern and four patients with fNSIP pattern was examined using two-dimensional gel electrophoresis and mass spectrometry. RESULTS By individually comparing each BALF sample, we found that the protein levels of surfactant protein A (SP-A), immunoglobulin heavy chain α, α-2 heat shock glycoprotein, haptoglobin β, and immunoglobulin J chain were significantly higher in the patients with UIP pattern than those in the patients with fNSIP pattern. In contrast, the protein levels of glutathione s-transferase, vitamin D-binding protein, and β-actin were significantly higher in the patients with fNSIP pattern than those in the patients with UIP pattern. To confirm the results of SP-A in the BALF proteome, we performed enzyme-linked immunosorbent assay in a larger group. The concentrations of SP-A in BALF from the patients with UIP pattern were significantly higher than those from the patients with fNSIP pattern (2.331 ± 1.656 μg/ml vs. 1.319 ± 1.916 μg/ml, p = 0.034). CONCLUSIONS We identified several proteins that may play roles in the development of pathological differences between UIP and fNSIP patterns of chronic HP.