Tropomyosin (TM), acting as heat-stable protein, has a high homology of amino acid sequences with different sensitizations. Fish belongs to vertebrate and its TM owns less allergenicity, whereas shrimp and clam belong to invertebrate and their TM are major allergens. Moreover, the allergenicity of TM might be altered during food processing. Therefore, shrimp-TM was administered intraperitoneally to BALB/c mice to establish an allergic mouse model, to evaluate the elicitation ability of these three proteins, while a mediator-releasing RBL cell line was used to estimate the variation in the stimulation abilities. The results showed that shrimp-TM owned stronger ability in the elicitation of the anaphylactic reactivity as well as in the IgE-mediated the RBL cell line. In comparison with shrimp-TM, clam-TM showed a similar allergic reaction and T-helper 2 (Th2)-based responses from spleen cells and mediums produced by RBL cell line, while fish-TM exhibited a weaker anaphylactic reactivity based on a mouse model and produced fewer active mediums based on cell model. Furthermore, raw and boiled TM did not exhibit a significant difference in allergic reactions and the capacity of degranulation. These results indicated that shrimp-TM owned stronger stimulation ability based on allergic mouse compared with fish-TM and clam-TM, which could supply information for clinical and anaphylaxis of TM in the stages of sensitization and simulation deserve further consideration.