Pulmonary delivery of nintedanib has noticeable advantages over the current oral administration in managing idiopathic pulmonary fibrosis (IPF). However, it remains a challenge to construct an efficient lung delivery system for insoluble nintedanib to resist nebulization instabilities and alveolar macrophage clearance. Herein, we attempted to develop nintedanib as inhalable nanocrystals stabilized with polysorbates. Different types of polysorbates (polysorbate 20, 40, 60, 80) and various drug-surfactant molar ratios (DSR = 10, 30, 60) were screened to determine the optimal nintedanib nanocrystal formulation. Most formulations (except those stabilized by polysorbate 40) could tailor nintedanib nanocrystals with sizes around 600 nm, and the nebulization-caused drug loss could be significantly reduced when DSR increased to 60. Meanwhile, all nanocrystals boosted the in vitro drug dissolution rate and improved the aerosol performance of nintedanib. Although nebulization-caused particle aggregation was found in most formulations, the nanocrystal stabilized with polysorbate 80 at DSR 60 presented no apparent size change after nebulization. This formulation exhibited superior alveolar macrophage evasion, enhanced fibroblast cluster infiltration, and improved fibroblast cluster inhibition compared with other formulations, indicating its significant potential for pulmonary nintedanib delivery. Overall, this study explored the potential of polysorbates in stabilizing nintedanib nanocrystals for nebulization and proposed practical solutions to transfer nintedanib from oral to lung delivery.