Objective To investigate the effect of sodium houttuyfonate on the expression of PI3K and AKT1 and mTOR mRNA in the lung of rats with chronic obstructive pulmonary disease (COPD), and reveal the possible mechanism of the COPD treated with sodium houttuyfonate. Methods Twenty-four male Wistar rats were randomly divided into normal control group, model control group, dexamethasone group and sodium houttuyfonate group (n =6 for each). The rat models of COPD were established by intratracheal instillation of lipopolysaccharide and smudging. The expressions of PI3K and AKT1 and mTOR mRNA were determined by real-time PCR. The morphological changes of the lung tissue was examined by histopathology. Results Compared with the normal control group, the expressions of PI3K and AKT1 were significantly increased and mTOR mRNA was significantly decreased in the model group ( P <0.01, P <0.05). Compared with the model group, the expressions of PI3K and AKT1 were significantly decreased and mTOR mRNA was significantly increased in the sodium houttuyfonate group and dexamethasone group( P <0.01, P <0.05). Compared with the dexamethasone group,the expression of mTOR mRNA was significantly increased in the sodium houttuyfonate group ( P <0.05). The pathological observation indicated that there were local pulmonary consolidation and a extensive neutrophil infiltration in the alveolar cavity. Prominent pulmonary interstitial fibrous hyperplasia was observed in the model group. The pathological manifestations were much ameliorated than those of the model group, and only mild interstitial pneumonia and a slight fibrous hyperplasia were seen in the sodium houttuyfonate and the dexamethasone groups. Conclusions Sodium houttuyfonate reduces the injury of lung tissue and has protective effect on COPD rats. The mechanism is probably related to the down-regulatation of expression of PI3K and AKT1 mRNA and up-regulatation of expression of mTOR mRNA in COPD rats.