Populus yunnanensis Dode., a native dioecious woody plant species in Southwest China, plays an important role in commercial forestry and environmental protection. In natural habitats, female P. yunnanensis trees are extremely rare while males are dominant in population. Our previous physiological studies in the species have revealed sex-dependent difference in response to drought stress, and females suffer greater negative effects than males. However, the molecular basis of sex-related differences during drought stress has been poorly characterized. We use the Illumina-Solexa platform to sequence the leaf transcriptomes derived from male and female P. yunnanensis trees grown in normal condition and drought stress. In total, 22,235 transcripts were identified in this study and 6039 genes were differentially expressed (DEGs) during drought stress. Majority of the DEGs were identified in males (92%, 5539); thus, males had greater remodeling of the leaf transcriptome in response to drought compared with females. Furthermore, many genes involved in hormone biosynthesis, photosynthesis and reactive oxygen species (ROS) scavenging enzyme system had more transcript changes in males than in females during drought stress, while these genes exhibited higher transcript alteration in females than in males in normal condition. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis of 15 selected genes suggested that during drought treatment the up-regulated DEGs had a quicker increment in their transcript abundances in females than that in males. The sexual differences of gene transcription coincide with the sexual different adaptation of P. yunnanensis in the present natural habitats.