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Immersion vaccination is dependent on the response of fish mucosa-associated tissues. Herein, javelin goby Synechogobius hasta was immersed with Vibrio vulnificus bacterin to investigate mucosal and humoral immune responses post-vaccination. The results showed that the specific serum antibody titers gradually increased after vaccination and peaked at day 21, while the mucosal antibody titers in the gill, skin, and intestine showed a faster response, with the peak time at days 3, 5, and 7, respectively. For antigen uptake, a rapid and significant enhancement was detected in the mucosa-associated tissues (gill, skin, and intestine) compared with the blood, spleen, kidney, and liver (P < 0.05). Antigen uptake levels in the gills and skin were peaked at 12 h post-immersion and were significantly higher than other tissues (P < 0.05). The histological results showed that the mucous cell numbers in mucosa-associated tissues increased over time, peaked at day 3 post-immunization, and then decreased to the level of the control groups. Additionally, the mucin components in mucosa-associated tissues shifted from neutral mucopolysaccharide to acidic mucopolysaccharide. Integrations of antibody titers, antigen uptake in mucosa-associated tissues, mucous cell number changes, and mucin characteristic changes provided valuable information for research on mucosal immunity in fish. All present findings suggest a major advantage of immersion vaccines to elicit a high level of local immune response, making immersion vaccines an ideal mode of inoculation that induces protective immunity against a variety of pathogens. [ABSTRACT FROM AUTHOR]