Objective This study aimed to investigate the effects of mitochondria division inhibitor-1（Mdivi-1）on cigarette smoke-induced airway inflammation and oxidative stress in mice and the possible mechanisms. Methods Mice were exposed to ciga⁃rette smoke to construct animal models of airway inflammation and oxidative stress，and midivi-1 was delivered by intraperitoneal injec⁃tion. The bronchoalveolar lavage fluid（BALF）was collected for cell counting analysis. The levels of TNF-α，IL-6，MMP-9 in BALF were detected by ELISA. The levels of oxidative stress，including MDA and the activity of SOD，in lung tissue homogenate，were deter⁃mined via biochemical kits. HE staining was used to evaluate the pathological changes of lung tissues. The possible genes Mdivi-1af⁃fected were searched in the PubChem database，followed by GO and KEGG analysis. Western blot was used to determine the expression changes of Drp1 and Mfn2 in the mouse lung tissue，and related enriched signal pathway. Results Cigarette smoke induced increased inflammatory cell infiltration，airway epithelial hyperplasia，airway epithelial thickening，and increased the number of total cells，neutro⁃phils，and macrophages in BALF. The levels of TNF-α，IL-6 and MMP-9 and oxidative stress were also increased，while pretreatment with Mdivi-1 could alleviate the above changes. 100 potential target genes of Mdivi-1 were retrieved by bioinformatic analysis，and GO analysis showed that they were enriched in biological processes of regulation of mitochondrion organization，apoptosis，and mitophagy， and KEGG analysis identified enriched signal pathways of Tnf，Mtor，Ampk，Adipocytokine and Nod-Like receptor. Western blot showed that pretreatment with Mdivi-1 could significantly inhibited the activation of NF-κB signaling pathway，down-regulated Drp1 expression and up-regulated Mfn2 expression in cigarette smoke-induced lung tissue of mice. Conclusion Mdivi-1 could alleviate airway inflammation and oxidative stress induced by cigarette smoke in mice，the mechanism of which might be achieved by improving mitochondrial function and inhibiting NF-κB signaling pathway. Thus，Mdivi-1 might be a novel drug for cigarette smoke-induced air⁃way diseases.