Non-small cell lung cancer(NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid(PLGA) large porous microparticle(LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2.72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGALPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly (lactic-co-glycolic) acid (PLGA) for about 85% of all lung cancers. Large porous microparticle (LPMP) for in situ treatment of NSCLC with the emulsion / solvent evaporation / freeze-drying method. Despite a geometric diameter of 10 mm, the aerodynamic diameter of the spheres was only 2. 72 mm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1 h, while the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without over phagocytosis. Rat Primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via air, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiog enesis inhibition and apoptosis. Relevance mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase- 9. The oridonin-loaded PLGALPMPs showed High conclusion of anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.