Leeches (family Hirudinidae) are classic model invertebrates used in diverse clinical treatments, such as reconstructive microsurgery, hypertension, and gangrene treatment. The blood-feeding habit is essential for these therapies, yet the molecular mechanisms underlying the process are poorly understood. In the present study, the transcriptome of Poecilobdella javanica from five time points (days 0, 1, 10, 20, and 30 separately) of blood feeding was sequenced with short paired-end reads. After stringent quality control, ∼380 million high-quality reads were assembled using SOAPdenovo-Trans with optimal parameters into a non-redundant set of 48 784 transcripts (≥100 base pairs), representing about 38 Mb of unique transcriptome sequence. The average length of the transcripts was 570 bp with N50 lengths of 5751 to 7413 bp among different time points. We have assessed the effect of sequence quality and various assembly parameters on the final assembly output. Functional categorization revealed the conservation of genes involved in various biological processes, such as basal transcription factors and ribosome biogenesis in eukaryotes. In addition, we found that DNA/RNA related pathways were predominantly expressed in the starving state while fatty acid metabolism, the anticoagulant pathway, and amino acid biosynthesis were activated during blood feeding. The leech transcriptome provides a resource for gene discovery and development of functional molecular markers during clinical applications.