Increasing evidences indicate that porcine circovirus type 2 (PCV2) is the causative agent of the post-weaning multisystemic wasting syndrome (PMWS). In this study, the prevalence of PCV2 infection in swine herds in southeastern China was investigated by ELISA and PCR, as well as the genetic characteristics by nucleic acid sequencing. Seroprevalence of PCV2 in samples collected from 89 swine herds was significantly higher by ELISA in post-weaning (54.1%) and growing piglets (49.9%) than that of suckling pigs (33.3%) with an average rate of 46.0% (819/1779). Seventy-eight cases out of 159 diseased pigs from these herds were PCV2 positive by PCR. Furthermore, the PCV2-positve rate at herds level in 2005 and 2006 were much higher than that in 2004 (65.63% or 69.23% vs. 32.26%, respectively), indicating that PCV-2 infection expanded rapidly over the past two years. To provide new insights into the extent of genetic heterogeneity of PCV2 isolates in southeastern China, the ORF2 genes of 27 isolates from the area during January 2004-March 2007 were sequenced and aligned. While closely related to each other with identity of 98.0-100%, these isolates displayed lower homologies to those from other regions of China (90.6-100%) or to some foreign isolates (91.3-98.9%). Alignment of deduced amino acid sequences of capsid protein identified two major hyper-variable regions (positions 53-91 and 185-215) in isolates obtained in this study, which were within or close to the putative epitope domains. The substitutions consequently resulted in higher hydrophilicity of the epitope region (positions 47-85). Phylogenetic analysis revealed two clusters of 48 isolates including those from Genbank: the large cluster I consisting of two subgroups and cluster II containing most of foreign isolates owing to the residue substitutions in epitope domains (amino acid positions 80, 86, 88 and 91). While the subgroup Ib contained all the isolates with ORF2 of 705 bp in length, the 27 isolates we sequenced were clustered exclusively in subgroup Ia together with some other Chinese strains. We conclude that PCV2 isolates prevailing in southeastern China were genetically different from those of other countries.