The outbreak of highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) in 2006 devastated Chinese swine industry.Up to now,compared with classical strain of PRRSV,HP-PRRS virus (HP-PRRSAO is still the predominant strain in mainland of China,and the attenuated live vaccine remains the preferable choice that could protect piglets against the HP-PRRSV infection.To fully evaluate the safety of the Modified Live Vaccine (MLV) virus- GDr180 strain,which is the 180th attenuated vaccine virus of HP-PRRSV GD strain clinicopathological,micropatholocial,ultrastructural pathological,serological and molecular biological methods were applied to assess the different responses and respiratory characteristics after piglets respectively inoculated with HP-PRRSV GD strain and GDr180 strain.The results revealed that piglets inoculated with GD strain appeared prominent clinical symptoms including pyrexia depression,anorexia,dyspnea and skin cyanopathy,significant interstitial pneumonia was characterized by thickened alveolar septa infiltrated with mononuclear cells and cell debris,while piglets inoculated with GDr180 strain and negative control piglets showed neither clinical symptoms nor microscopic and ultrastructral lesions.Furthermore,ultrastructral observation on tracheas,dynamic distribution of antigen examined with both Immunohistochemistry (IHC) and fluorescent quantitative RT-PCR (FQ-RT-PCR) all verified that there were significant differences between PRRSV GD strain and GDr180 strain on pathogenicity and virus distribution in the respiratory system of piglets.This difference in pathogenicity was helpful in explaining the variation in severity of pathology changes observed between pigs inoculated with HP-PRRSV GD strain and its attenuated vaccine.Therefore,HP-PRRSV GDr180 vaccine strain was utterly inoffensive to respiratory system of piglets,and may be the applicable vaccine candidate to withstand HP-PRRS.