The present study investigated the role of the endogenous cystathionine gamma-lyase (CSE) / hydrogen sulfide pathway in the pathogenesis of pulmonary fibrosis. Rats treated with intratracheal bleomycin were exposed either to the H2S donor NaHS or to saline. The results on day 7 showed that plasma H2S concentration and pulmonary CSE activity (H2S production rate) were significantly lower in rats treated with bleomycin and saline (fibrosis-alone) than in controls, whereas on day 28 plasma H2S concentration was higher and pulmonary CSE activity was the same as that of controls. The relative CSE mRNA level in the lungs of rats treated with bleomycin was significantly higher than control values on days 7 and 28. After exposure to NaHS, the total lung hydroxyproline content and the malondialdehyde (MDA) content were both significantly lower, with no difference observed between NaHS high-dose and low-dose treatments. Further, MDA formation stimulated by the free radical-generating system (FRGS) in vitro was lower in lung tissue incubated with NaHS than it was in tissue incubated with FRGS alone. These results suggest that NaHS administration ameliorated the pulmonary fibrosis induced by bleomycin in rats and that this protective effect of H2S may be mediated by its antioxidative action.