Antimicrobial proteins/peptides are becoming a new generation of immunostimulants for prevention and disease control in human and animals, including aquatic animals. As the haemolymph of horseshoe crabs (Tachypleus) contains broad ranges of bioactive compounds, we have explored the in vivo immunostimulating potential of amoebocyte lysate and plasma using a fish model. Indian major carp, Labeo rohita, yearlings were injected intraperitoneally with two doses of lysate and plasma at 50 and 100 µg protein per fish. No abnormalities and/or mortalities were recorded in any group. L. rohita injected with 50 µg lysate and 100 µg plasma protein showed significant enhancement (P < 0.01) of various haematological and immunological parameters. There was a significant rise in the total protein and globulin content, myeloperoxidase and respiratory burst activity following injection with 50 µg lysate and 100 µg plasma protein. The agglutinating and haemagglutinating activities were increased albeit not significantly (P > 0.01) in any groups. On the contrary, a significantly high hemolysin titre was recorded in fish that received 100 µg plasma protein. Following challenge with Aeromonas hydrophila, both lysate and plasma protein(s) cross protected the fish after 30 days. The highest survival (50%) was recorded in group injected with 50 µg lysate protein, followed by 45% in both 100 µg lysate and plasma protein injected groups.