INTRODUCTION: As a chronic, progressive, and lethal pulmonary disease, chronic obstructive pulmonary disease (COPD) is lacking effective treatment. Chronic inflammatory processes, including inflammatory cytokines, play an important role with in its pathogenesis. Jianpiyifei (JPYF) granule is a traditional Chinese herbal formula historically used to strengthen the spleen and tonify the lung. JPYF is used clinically to treat stable COPD. However, whether the purported anti‑inflammatory effect of JPYF in COPD involves regulation of key inflammatory cytokines is not clear.MATERIALS AND METHODS: The mice model of pulmonary inflammation was induced by lipopolysaccharide (LPS) and cigarette smoke condensate (CSC). The influence of JPYF on airway inflammation in vivo was investigated. Mice were divided into three groups: control, model, and treatment groups. In the CSC + LPS model group and JPYF treatment group, intratracheal injection of CSC and LPS was used to induce airway inflammation for 5 days. JPYF group animals were also orally administered 5.5 g/kg JPYF granule for 12 days.RESULTS: The number of neutrophils and total cells in bronchoalveolar lavage fluid of the JPYF group were markedly lower than in the model group. The levels of interleukin (IL)‑1 β and IL‑6 were lower; tumor necrosis factor‑alpha was downregulated, and IL‑10 was higher in the JPYF group than the model group. In the JPYF group, histone deacetylase 2 (HDAC2) activity and protein expression were restored.