OBJECTIVE: To study the effects of ulinastatin on pathological state of lung tissue and aquaporin 1 (AQP-1) and matrix metalloproteinases (MMP-2), MMP-9 expressions in silicosis rats. METHODS: Wistar rats were divided into normal control group, model group, ulinastatin high-dose, medium-dose, low-dose groups (50×104, 10×104, 2×104 u/kg), 20 in each group. Except for normal control group, rats in other groups were given 40 mg/mL SiO2 suspension 1 mL by non-exposed endotracheal perfusion to induce silicosis model; 1 h before modeling administration, corresponding doses of ulinastatin were intraperitoneally injected, for 3 d. Hematoxylin-eosin staining was used to observe silicon nodules in lung tissue of rats in each group; immunofluorescence method was used to detect AQP-1 expression in lung tissue; real-time fluorescence quantitative polymerase chain reaction method was used to detect MMP-2, MMP-9 mRNA expressions in lung tissue; Western blot method was used to detect MMP-2, MMP-9 protein expressions in lung tissue. RESULTS: There were obvious silicon nodules and serious structural damage in lung tissue in model group, ulinastatin groups showed macrophage foci visible dust, but pulmonary fibrosis was obviously reduced. Compared with normal control group, AQP-1 expression in lung tissue in other groups were reduced, MMP-2, MMP-9 mRNA and protein expressions were enhanced (P<0.05). Compared with model group, AQP-1 expression in lung tissue in ulinastatin groups were increased, MMP-2, MMP-9 mRNA and protein expressions were decreased (P<0.05), in which improvement effects in high-dose, medium-dose groups were superior to low-dose group (P<0.05). CONCLUSIONS: Ulinastatin can reduce the pathological state of silicosis rats, increase AQP-1 expression and decrease MMP-2, MMP-9 expressions.