Abstract: Objective To investigate the mechanism of liver-soothing and stomach-harmonizing recipe alleviating airway inflammation in rats with gastroesophageal reflux disease (GERD) by regulating peroxisome proliferator-activated receptor γ/retinoid X receptor (PPAR-γ/RXR) signaling pathway. Methods A rat model of GERD with airway inflammation was established by perfusion of hydrochloric acid into the lower esophagus. A total of 50 SD male rats were randomly divided into control group, model group, low-dose liver-soothing and stomach-harmonizing recipe group (10.49 g/kg crude drug dosage), high-dose liver-soothing and stomach-harmonizing recipe group (20.98 g/kg crude drug dosage), and omeprazole group (3.67 mg/kg), with 10 rats in each group. The rats were gavaged for 14 days. Hematoxylin and eosin (HE) staining was used to observe the pathological change in tracheal tissue. RT-qPCR was used to detect the mRNA expression levels of inflammatory cytokinesinterleukin (IL)-17, IL-33, inducible nitric oxide synthase (iNOS)and anti-inflammatory cytokinesIL-10, Clara cell 16-kDa protein (CC16), surfactant protein-D (SP-D)in bronchoalveolar lavage fluid; the Western blot was used to detect the relative protein expression levels of PPAR-γ, RXR-α, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1). Results The HE staining results showed that a large number of inflammatory cell infiltrations were observed in the model group, while the inflammatory cell infiltrations were significantly reduced in the low-dose liver-soothing and stomach-harmonizing recipe group, high-dose liver-soothing and stomach-harmonizing recipe group, and omeprazole group. Compared with the control group, the mRNA expression levels of IL-17, IL-33 and iNOS in bronchoalveolar lavage fluid were significantly increased while the mRNA expression levels of IL-10, CC16 and SP-D were significantly decreased in the model group, and the relative protein expression levels of PPAR-γ and RXR-α were significantly increased, while the relative protein expression levels of NF-κB and AP-1 were significantly decreased in the model group (P<0.05). Compared with the model group, the above indicators were significantly improved in the high-dose liver-soothing and stomach-harmonizing recipe group and omeprazole group (P<0.05). Conclusion Liver-soothing and stomach-harmonizing recipe can effectively alleviate airway inflammation in rats with GERD, and its mechanism may be related to the activation of the PPAR-γ/RXR signaling pathway.