OBJECTIVES: The purpose of the present study was to clarify the consecutive changes and roles of hyaluronan (HA), interleukin-8 (IL-8) and collagen production by lung fibroblasts in the course of pulmonary fibrosis. METHODS: Quantitative and comparative assessments of the HA, IL-8 and collagen (presented by hydroproline; HYP) levels in lung fibroblast-conditioned media were made at various stages during the development of bleomycin-induced pulmonary fibrosis in rats. RESULTS: In lung fibroblast-conditioned media of bleomycin-treated animals: (1) The HA levels increased significantly on day 1, peaked on day 3, and then gradually declined and returned to control values on days 14 - 28. (2) The IL-8 levels strikingly increased on day 1, reached the peak values on day 7, thereafter, gradually decreased, regained control values by day 28. (3) The collagen levels increased significantly on day 7, peaked on day 14, and then gradually declined, However, remained significantly above normal values on day 28. (4) In bleomycin group, the HA and IL-8 levels both significantly correlated to cell components in BALF. CONCLUSIONS: The lung fibroblasts were activated, produced increased HA and IL-8, and were the main source of HA and IL-8 within the lung in the early stage of pulmonary fibrosis; increased HA and IL-8 synthesis of lung fibroblasts might reflect the intensity of alveolitis and the disease activity; The excessive collagen deposition within the lung primarily occurred at the middle stage of pulmonary fibrosis.