Edwardsiella tarda is a versatile pathogen that could survive in different environmental conditions and infect economically important fish species. The whole cell antigenic proteins were extracted from E. tarda and assessed via Western blot using anti E. trada rohu and anti E. trada rabbit serum. Two strong reacted proteins with antibodies were recovered viz 61 kDa and 47 kDa from SDS PAGE gels to evaluate their vaccine potential in rohu fish. Fish were vaccinated 10 µg of antigenic proteins intraperitoneally as immunogens with Freund’s incomplete adjuvant (FIA). The boosters were given on the 10^th day of immunization with PBS. The blood was drawn from vena caudalis at every 7^th day for hematological and immunological studies. Fish were challenged on 35^th day with 1× 10⁶ cfu E. tarda field isolate ET-1. The cumulative mortality (CM) was recorded over one week and relative percentage survival (RPS) was calculated. The 61 kDa and 47 kDaproteins had significantly higher RPS, white blood cell count, specific and nonspecific parameters over control group. 61 kDa protein gave significantly high NBT activity, lysozyme activity and specific antibodies for E. tarda. 47 kDa protein hadsignificantly high phagocytic index and myeloperoxidase activity. The phagocytic capacity was significantly high at 3^rd week of 47 kDaprotein. 61 kDaand 47kDa proteins had RPS of 59% and 52% respectively after challenge studies. Non specific immune parameters were more active at the first four weeks of immunization and specific antibodies for E. tarda were significantly higher since second week and peaked at 4^th week in this study. Therefore 61 kDa could be considered as best vaccine candidateover 47 kDa for E. tarda infection in rohu fish.