Objective To explore the therapeutic effect and mechanism of Qingfei Touxie decoction on mice with Mycoplasma pneumoniae (MP). Methods Forty male specific-pathogen-free BALB/ c mice were randomly divided into the control, model, low-dose, medium-dose, and high-dose Qingfei Touxie decoction groups, with n = 8 mice per group. A mouse model of MPP was established via nasal instillation of solution containing MP. Mice in the model and control groups received 0. 9% saline solution by oral gavage, and mice in the Qingfei Touxie decoction (QFTXT)-treated groups received QFTXT at low (200 mg / kg body weight), medium (400 mg / kg body weight) and high (800 mg / kg body weight) doses daily. After 2 weeks of treatment, the lung tissue indices of the mice were calculated, and the pathological changes in the lung tissue were observed via hematoxylin and eosin staining. Apoptosis in the mouse lung cells was detected via TUNEL staining, and the interleukin (IL)-1β, TNF-α, IL-6, and IL-18 levels were detected using enzyme-linked immunosorbent assays. NLRP3, MyD88 and NF-κB mRNA expressions in the lung tissue were detected using qPCR, and the NLRP3, MyD88 and p-NF-κB protein expressions in the lung tissue were detected via western blot. Results Qingfei Touxie decoction significantly reduced the lung indices of the MPP mice and reduced the lung pathological damage and apoptotic rates (P< 0. 05). Qingfei Touxie decoction also significantly reduced the IL-1β, TNF-α, IL-6 and IL-18 levels ( P< 0. 05) and NLRP3, MyD88 and NF-κB mRNA and protein expressions ( P< 0. 05). Conclusions Qingfei Touxie decoction attenuated lung injuries in mice with MP pneumonia, possibly by inhibiting NLRP3 inflammatory bodies and the NF-κB signaling pathway.