Objectives To investigate the effects of cryptotanshinone (CTS) on cigarette smoke (CS) -induced airway inflammation and oxidative stress in mice and the possible mechanisms. Methods BALB/c mice were exposed to CS for 4 weeks to establish airway inflammation model. CTS was given by intraperitoneal injection before CS exposure at a dosage of 30 mg·kg−1·d−1 or 15 mg﹒kg−1·d−1. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and detection of pro-inflammatory cytokine [interleukine (IL)-17, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α] levels. Lung tissue was collected for histological examination, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, immunohistochemistry and polymerase chain reaction for Muc5ac detection, and western blot for lectin-like oxidized low-density lipoprotein-1 receptor (LOX-1) and nuclear factor (NF)-κB. Results CTS administration attenuated CS exposure induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction, increased numbers of total cells, macrophages, and neutrophils, and decreased the releases of IL-17, MCP-1, TNF-α in BALF of mice. CS exposure could induce the elevation in MDA levels and decrease in SOD activities, markers of oxidative stress. CTS could attenuate these changes. CTS also attenuated CS induced up-regulation of the protein levels of LOX-1 and phosphorylated p65, down-regulation of the levels of NF-κB inhibitor α. Conclusion CTS alleviates the airway inflammation, oxidative stress and mucus hypersecretion induced by CS, which may be through the regulation of LOX-1 and NF-κB signaling pathway.