Newcastle disease (ND) is one of the most serious viral diseases affecting poultry farms in different countries. Many outbreaks -even in vaccinated poultry flocks- were recorded in the last few years caused by Newcastle disease virus (NDV) genotype VII. This study was conducted to compare the pathogenesis of NDV genotype VII in non-vaccinated chickens and chickens vaccinated with NDV genotype II live (LaSota) and inactivated vaccines. One hundred 1-day-old chicks were divided into four equal groups; 25 for each. Groups A and B were kept unvaccinated. Group C was vaccinated with LaSota, and group D was vaccinated with both LaSota and inactivated NDV vaccine. Group A was kept as nonchallenged control blank group, while groups B, C and D were challenged intranasally by 0.1 ml 106 EID50 NDV genotype VII at 25-day of age. Three chickens were sacrificed from each group at 2, 5- and 10-days post challenge (dpc). Tissue specimens from trachea, lungs, bursa of fabricius, spleen and thymus were collected for histopathology and immunohistochemistry. NDV genotype VII challenge virus did not induce mortality in both vaccinated groups. Both vaccination programs resulted also in less severe clinical signs and histopathological lesions comparing to non-vaccinated challenged birds. Tracheal lesion score was significantly low in group D at 10 dpc while no significant difference was recorded between groups C and D in lungs. All lymphoid organs showed significantly less severe pathological alterations and depletion in groups C and D comparing to group B. Our results indicated that mis-matched genotype NDV vaccines could alleviate the pathological effect of the NDV challenge virus but do not provide complete protection of the infected host organs.