In order to further study the pathogenesis of highly pathogenic porcine reproductive and respiratory syndrome virus（HP-PRRSV），the histopathological changes of natural and artificial infection with HP-PRRSV were compared and observed. For the nature of lesions，the natural and artificial infection cases were basically similar，but obviously different in the scope and severity degree of the lesions；the gastrointestinal lesions were particularly significant in the natural infection cases，and fewer gastrointestinal lesions were observed in the artificial ones；all the lymph nodes were involved in the inflammation of the natural infection cases，but the lesions of hilar lymph nodes，mandibular lymph nodes and mesenteric lymph nodes appeared in the artificial infection cases，and other lymph nodes were normal. Mixed infection with multiple diseases were common in natural infection cases，indicating that HP-PRRSV might be the general cause for several diseases. Severe interstitial pneumonia was shown in the lungs of both natural and artificial infection cases，which indicated that the pathological changes of the lungs were indicative for the diagnosis of single infection with HP-PRRSV. As a conclusion，a theoretical basis was provided for the diagnosis of HP-PRRSV infection and for the study on its pathogenesis.