Abstract:【Abstract】 Objective To observe the effect of intermittent normobaric hypoxia on the expression of Transforming Growth Factor beta1 (TGFβ1), Smad4, collagen I(Col I), Tumor Necrosis Factor alpha(TNFα) and on the changes in the histological structure of the Rats’ Lung and the effect of breviscapine on the hypoxiainduced changes. Methods 80 Rats were randomly divided into control group (group A), hypoxia group (group B), hypoxia and lowdose breviscapine group (group C), hypoxia and highdose breviscapine group (group D). They were placed in normal environment or intermittent normobaric hypoxia (101kpa,10% O2, 8h every day), respectively. At the 3d, 7th, 14th, 21st day, 5 rats from each group were killed, Hematoxylin and Eosin staining (HE staining) was taken to observe the pathological change in the rats’ lung, Immunohistochemical staining to detect the protein level of TGFβ1, Col I and Western blot to detect the expression of Smad4. RTPCR was performed to detect the mRNA levels of TGFβ1 and Col I. Besides, the TNFαin the bronchoalveolar lavage fluid (BALF) were determined by ELISA. Results HE staining shown that mild edema and inflammatory cell infiltration appear in the lung tissue at the 3d day, meanwhile inflammation gradually aggravated, and the interalveolar septum became thicker and thicker as the time of exposing to hypoxia going on. In both breviscapine groups, the degree of hypoxiainduced inflammation and the septum changes were lighter than that in the hypoxia group. Compared with the normoxia group, not only the protein expression of TGFβ1, Smad4,Col I and TNFα, but also the mRNA expression of TGFβ1and Col I were elevated, and with longer exposure to hypoxia they increase further. It also demonstrated positive correlation between the protein level of TGFβ1 and Smad4. Meanwhile the protein of TGFβ1, Smad4, Col I, TNFα and Col I mRNA detected in both the breviscapine groups were declined. The expression level in group D was lower than group C. There is no statistical difference in TGFβ1mRNA in the three groups, B,C and D. Conclusion Via inducing pulmonary edema and inflammation, upregulating expression of TNFαand activating the TGFβ1/Smads Signaling Pathway, hypoxia induces the synthesization of Col I increase, extracellular matrix deposite and interalveolar septum thicken. While breviscapine maybe can inhibit the TGFβ1/Smads Signaling Pathway, decrease the expression of TNFαand Col I and protect the lung from tissue remodeling.