AIM: To investigate the effect of scutellarin combined with polydatin on pulmonary and bronchial injury induced by lipopolysaccharide (LPS) combined with smoking in rats and its mechanism. METHODS: Male SD rats were randomly divided into control group, model group, Huangqin Jingye-Huzhang decoction (5 g/kg) group, scutellarin (40 mg/kg) group, polydatin (60 mg/kg) group, scutellarin+polydatin (20 mg/kg+30 mg/kg, 40 mg/kg+60 mg/kg and 80 mg/kg+120 mg/kg) groups, and Guilong Kechuanning tablet (1 g/kg) group, with 10 rats each group. Chronic bronchitis model was established in 90 rats. The levels of interleukin-1β( IL-1β), IL-6, IL-17A, IL-10 and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and serum were measured by ELISA, and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were detected using kits. Protein content and cell counts in BALF were determined. Wet/dry( W/D) mass ratio of the right lung was estimated, and HE staining was used to observe the pathological changes of pulmonary and bronchial tissues and score the lung tissue injury. The mRNA expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mammalian target of rapamycin (mTOR) was detected by RT-qPCR. The protein levels of p-PI3K, PI3K, p-AKT, AKT, p-mTOR and mTOR were detected by Western blot. RESULTS: Compared with control group, the levels of IL-1β, IL-6, protein, leukocytes and neutrophils in BALF, the levels of IL-17A and TNF-α in serum, the content of MDA in lung tissues and the W/D mass ratio of the right lung in model group were significantly increased (P<0. 01), while the content of IL-10 in serum and the activity of SOD in lung tissue were significantly decreased( P<0. 01). The protein levels of p-PI3K, p-AKT and p-mTOR were significantly up-regulated (P<0. 01). Compared with model group, the levels of IL-1β, IL-6, protein, white blood cells and neutrophils in BALF, the levels of IL-17A and TNF-α in serum, the content of MDA in lung tissues and the W/D mass ratio of the right lung in scutellarin+polydatin (20 mg/kg+30 mg/kg, 40 mg/kg+60 mg/kg and 80 mg/kg+120 mg/kg) groups were significantly lower than those in model group( P<0. 01 or P<0. 05), while the content of IL-10 in serum and the activity of SOD in lung tissue were significantly increased (P<0. 01). The pulmonary and bronchial inflammatory response was alleviated, and the injury was obviously attenuated. The protein levels of p-PI3K, p-AKT and p-mTOR were significantly down-regulated (P<0. 01). CONCLUSION: Scutellarin combined with polydatin protects pulmonary and bronchial tissues against the injury induced by LPS combined with smoking in rats. The mechanism may be related to inhibiting the activation of PI3K/AKT/mTOR pathway, reducing oxidative stress and inhibiting inflammatory factors such as IL-17A, TNF-α, IL-1β and IL-6. [ABSTRACT FROM AUTHOR]