Like other important cereal crop in modern agricultural production, maize is also threatened by drought. And the drought stress during maize filling stage will directly affect the quality (protein or oil concentration) and also the weight of grain. Therefore, different from previous studies focusing on inbred lines and pot experiment at seedling stage, current study selected filling stage of the adult plant and planting maize in the experimental field. Two hybrids cultivars with different drought tolerant were used for drought and water treatment respectively. We performed transcriptome sequencing analysis of 4 groups, 12 samples, and obtained 651.08 million raw reads. Then the data were further processed by mapping to a reference genome, GO annotation, enrichment analysis and so on. Among them we focus on the different change trends of water treatment and drought treatment, and the different responses of two drought-tolerant cultivars to drought treatment. Through the analysis, several transcripts which encode nitrogen metabolic, protein phosphorylation, MYB,AP2/ERF, HB transcriptional factor, O-glycosyl hydrolases and organic acid metabolic process were implicated with maize drought stress. Our data will offer insights of the identification of genes involved in maize drought stress tolerance, which provides a theoretical basis for maize drought resistance breeding.