Abstract: New castle disease (ND) is one of the most serious infection diseases that damage ostrich cultivation. As a stressor, ND could invade the organism and cause a series of pathological changes in body, which induced excessive activation or inactivation of ostrich chicks' hypothalamuspituitaryadrenocortical axis (HPA), and seriously disturbs the organismic internal environment. In the present study, ostrich chicks aged 45 days were divided into normal group and challenge group at random. The methods of HE staining, transmission electron microscopy (TEM)，and immunohistochemistry (SABC) were used to study the changes of morphology and theγaminobutyricacid (GABA) expression in ostrich chicks’ HPA axis with challenge by Newcastle disease virus（NDV）. The results are as follows: The ostrich was highly sensitive with NDV, which can cause significant change on histopathology of HPA axis. The adrenalopathy worsened seriously, followed by hypothalamus, and a pituitary disease was a little lighter, which reflected the damage degree of the HPA. (2) Infected with NDV, the GABA expression of HPA axis in ostrich downgraded, change regularity in adrenals shows that GABA may participate in stress reaction of HPA axis which was caused by ND. The expression in the number and intensity of is related to pathological stress reaction.