ABSTRACT: BACKGROUND: The highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) emerging in China exhibits high fatality to pigs. However, the mechanism related to the increased pathogenicity of the virus remains unclear. In the present study, the differences in tissue tropism between the highly pathogenic PRRSV strain (JXwn06) and the low pathogenic PRRSV strain (HB-1/3.9) were investigated using PRRSV-specific immunohistochemistry (IHC) staining to provide evidence for elucidating possible mechanism of the pathogenicity of Chinese highly pathogenic PRRSV. FINDINGS: IHC examination showed that PRRSV antigen in the tissues including spleen, tonsil, thymus, kidney, cerebellum, stomach, small intestine, large intestine, turbinal bone and laryngeal cartilage was positive in more pigs inoculated with JXwn06 than HB-1/3.9, and the tissues including trachea, esophagus, liver, mandibular gland and thyroid gland were positive for viral antigen in the pigs inoculated with JXwn06, but not in the pigs inoculated with HB-1/3.9. Meanwhile, we observed that epithelium in tissues including interlobular bile duct in liver, distal renal tubule of kidney, esophageal gland and tracheal gland were positive for viral antigen only in JXwn06-inoculated pigs, and epithelium of gastric mucosa and fundic gland, and intestinal gland were positive for viral antigen in both JXwn06- and HB-1/3.9-inoculated pigs, using monoclonal antibodies to N and Nsp2 proteins. CONCLUSIONS: Taken together, these findings indicate that the highly pathogenic PRRSV JXwn06 displays an expanded tissue tropism in vivo, suggesting this may contribute to its high pathogenicity to pigs.