This study was conducted to assess efficacy of heat stable I2 vaccine against Newcastle diseases in vaccinated and vaccinated-in contact chickens following challenge againstvirulent ND virus (JF820294.1) in village chicken. And to assess whether birds that have been exposed to vaccine virus-shedding birds were protected against mortality and clinical signs after infection with a virulent strain of the NDV. 150 one-day old local chickens were divided into seven groups (4 experimental groups of 30 birds and 3 control groups (unvaccinated unchallenged, challenged, just vaccinated). In experimental groups birds were vaccinated either via drinking water or as food carrier with thermostable I-2 vaccine and then challenged with virulent isolate of NDV (JF820294.1), 8 birds were added as in-contact birds to vaccinated groups. Following challenge 7 extra birds were added to all groups as in-contact with vaccinated and challenged birds. Survival rate, clinical signs, necropsy finding and mean antibody titer were evaluated in different experimental and control groups. Birdsvaccinated via drinking water showed almost 100% survival rate. In this study the acute phase protein include TNF-?and IFN-?, haptoglobin (Hp) and serum amyloid A (SAA) and gangliosides (total sialic acid (TSA), lipid-bound sialic acid (LBSA) and protein-bound sialic acid (PBSA) using validated standard procedures were evaluated.All measured parameters, except Hp showed significant differences from the baseline level in different days post challenge. However birds vaccinated with food carrier vaccine, showed less than 50% survival rate. The in-contact birds in vaccinated and challenged groups via drinking water become seropositive, but did not show any advert clinical signs and necropsy lesions.The use of ND Thermostable I-2 vaccine in village chicken prevented of mortality and reduced APP concentration.