The present study was conducted to evaluate the immune-stimulating effect of CpG-ODN (Toll-like-receptor-agonist21) on broiler chickens vaccinated against Newcastle disease. The motifs were examined with different vaccination programes using different inoculation routes. 270 (one-day-old) - chicks were divided into 6 groups. Group one as a negative control sham inoculated with PBS; group two was injected intramuscularly with CpG-ODN; group three was vaccinated with live ND vaccine by eye-drop route; group four was vaccinated by eye-drop route and injected with CpG-ODN; group five was vaccinated with Newcastle disease inactivated vaccine and injected intramuscularly with CpG-ODN; group six was vaccinated by eye-drop route with live attenuated vaccine dissolved in CpG-ODN. Antibodies responses were monitored based on hemagglutination inhibition test and ELISA assay for the detection of IgG. The average body weight gain and feed conversion ratio were estimated to evaluate CpG-ODN growth-promoting effect. All vaccinated groups supplied with CpG-ODN recorded higher antibodies titer than the only vaccinated group. Group 4 which vaccinated and inoculated intra-muscularly with CpG-ODN recorded higher antibodies titer than other vaccinated groups. Antibodies titer was similar in group five and six without significant difference and both were lower than group 4. ELISA assay confirmed the significance between the adjuvanted groups at 21 and 35 days old. There were no significant differences (p≥0.05) observed between the vaccinated and adjuvated groups in either average body weight gain or in feed conversion rate. In conclusion, CpG-ODN proved its efficiency as an adjuvant when co-inoculated with Newcastle disease vaccines via different administration routes.