This study included one hundred and fifty one day old chicks divided into five groups each group contain 30 chicks G1 control negative , G2 control positive (deionized water), G3 Intranasal vaccine with CS-NPs, G4 Intranasal vaccine with NDV (La Sota), G5 Intranasal vaccine with NDV-CS-NPs(EID50:107.5), each groups were vaccinated at 10 and 21 days old, blood samples were collected at 16 , 26 and 30 days old and examined by ELISA, the highest IgA level were in G5 (21.87 pg/ml) at 30 day old chicks. The infectivity of virulent ND virus were used to measure the titration of 70 embryonated eggs at ten-days old embryonated chicken eggs, the lethal dose (LD50) of local ND virus and the result was 107.34/1ml. G5 chickens vaccinated with the NDV-CS-NPs vaccine were completely protected against the ND virus challenge, while the chicks in G1 were dead following the virulent NDV challenge and displayed clinical signs such as conjunctivitis, sudden death, and ruffled feathers, as well as postmortem lesions such as hemorrhage the many positions of the trachea, caecal toncil, and on the tips of glands in proventiculus. These findings suggest that, in comparison to regular and nano-chitosan, the use of Newcastle disease vaccine-chitosan nanoparticles in experiment two (in group 5) produced a stronger immune response and better protection.