MOTIVATION: The next-generation high-throughput sequencing technologies, especially from Illumina, have been widely used in re-sequencing and de novo assembly studies. However, there is no existing software that can simulate Illumina reads with real error and quality distributions and coverage bias yet, which is very useful in relevant software development and study designing of sequencing projects. RESULTS: We provide a software package, pIRS (profile-based Illumina pair-end reads simulator), which simulates Illumina reads with empirical Base-Calling and GC%-depth profiles trained from real re-sequencing data. The error and quality distributions as well as coverage bias patterns of simulated reads using pIRS fit the properties of real sequencing data better than existing simulators. In addition, pIRS also comes with a tool to simulate the heterozygous diploid genomes. AVAILABILITY: pIRS is written in C++ and Perl, and is freely available at ftp://ftp.genomics.org.cn/pub/pIRS/.