In order to establish a piglet disease model of Haemophilus parasuis（HPS），the virulence on piglets was determined by the strains of HPS serotypes 4（SD-05 and ZC-7）and 5（HB-08 and PZ-26），then the optimal strains of the two serotypes were injected respectively and intraperitoneally into healthy and susceptible weaned piglets aged 21 to 28 days old at the optimal dose to observe their clinical symptoms and pathological changes，followed by bacterial isolation and identification by PCR on dead piglets. The results showed that the strains of serotypes 4（SD-05）and 5（HB-08）were with strongest virulence at the optimal doses of 4.8×109 CFU and 4.7×109 CFU respectively. Clinical symptoms such as depression，dyspnea，cough，emaciation，claudication，visible mucosal cyanosis，etc.，were observed in the challenged piglets，and pathological changes such as fibrinous exudates from surface of visceral organs and within pleuroperitoneal cavities，“trichocardia”appeared in hearts were observed through autopsy. The strains of HPS serotypes 4（SD-05）and 5（HB-08）were successfully isolated from tissues and organs of piglets. It was concluded that a disease model for piglets infected with HPS serotypes 4 and 5 was established in the study，which laid a foundation for future study on the pathogenesis，diagnosis and immunity against HPS.