The aim of this study was to investigate the mechanism of abnormal SPA expression after smoke inhalation injury (SII).The rat model with SII was used to observe the expression of SPA and the level of H 2 O 2 in the lung tissue. EMSA was performed to study the effect of H 2 O 2 on the TTF 1 binding activity in regulating area of SPA gene. The results showed that H 2 O 2 was increased, and the expression of SPA was down regulated in lung tissue after smoke inhalation injury. H 2 O 2 could inhibit the TTF 1 binding activity in SPA regulating area in vitro . Our results suggested that the inhibition of TTF 1 activity by oxidative stress might be the mechanism of abnormal SPA expression after SII.