Serological cytokine profile was studied in native Nicobari fowl of A&N Islands and its comparative evaluation was carried out in other local poultry population. Blood was collected from 150 poultry comprising 30 samples each of Nicobari fowl, commercial layer and broilers, desi bird and Vanaraja poultry. The concentration of cytokines viz. chicken interferon alpha and beta (IFN-α and IFN-β) (ng/L), chicken interleukin- 6 (IL-6) (ng/L), chicken interleukin-12 (IL-12) (pg/ml), chicken toll like receptor (TLR 4) (ng/ml) and chicken major histo-compatibility complex MHC (ng/ml) were determined by immunoenzymatic assay (ELISA). Results revealed that the concentrations IFN-α and IFN-β in serum is significantly higher in commercial layers that was statistically at par with Nicobari fowl. The cytokine, IL- 6 was significantly lowest in native Nicobari fowl and desi birds and highest in broilers and vanaraja birds. Significantly higher serum concentration of IL-12 was recorded in Nicobari fowl and it was statistically comparable with desi birds and broilers. Level of TLR4 in serum was significantly highest in broilers followed by commercial layers and Nicobari fowl. Commercial broilers, layers and vanaraja birds have significantly higher level of MHC followed by Nicobari fowl. Hence it can be concluded that the higher concentrations of serum IFN-α and β, IL-12, TLR4 and MHC in native Nicobari fowl indicates their innate immunological balance that maintain immune homeostasis and enhances immune function and resistance to disease by stimulating T and B lymphocyte formation modulating cytokine secretion profiles.