Lodging is a major problem limiting maize yield worldwide. However, the mechanisms of lodging resis-tance remain incompletely understood for maize. Here, we evaluated 443 maize accessions for lodging resistance in the field. Five lodging-resistant accessions and five lodging-sensitive accessions were selected for further research. The leaf number, plant height, stem diameter, and rind penetrometer resis-tance were similar between lodging-resistant and-sensitive inbred lines. The average thickness of scle-renchymatous hypodermis layer was thicker and the vascular area was larger in the lodging-resistant lines compared with lodging-sensitive lines. Although total lignin content in stem tissue did not signif-icantly differ between lodging-resistant and-sensitive lines, phloroglucinol staining revealed that the lig-nin content of the cell wall in the stem cortex and in the stem vascular tissue near the cortex was higher in the lodging-resistant lines than in the lodging-sensitive lines. Analysis of strand-specific RNA-seq tran-scriptome showed that a total of 793 genes were up-regulated and 713 genes were down-regulated in lodging-resistant lines relative to lodging-sensitive lines. The up-regulated genes in lodging-resistant lines were enriched in cell wall biogenesis. These results indicated that modification of cell wall biosyn-thesis would contribute to lodging resistance of maize.