A 4-week feeding trial was conducted to determine the effects of different dietary supplements on the growth, immunity and resistance of sea cucumber Apostichopus japonicus against Vibrio splendidus infection. The control group was supplied with blank microcapsules, and Astragalus polysaccharide (APS) microcapsules, tuckahoe polysaccharide (TPS) microcapsules, (APS ? TPS) microcapsules, (APS ? TPS) microcapsules ? Bacillus subtilis, were tested for effects. Coelomic fluid was collected at 7-day intervals to test activities of lysozyme (LSZ), superoxide dismutase (SOD), alkaline phosphatase (AKP), and complement 3 (C3) content. After the feeding trial, the specific growth rate of sea cucumbers fed a diet supplemented with (APS ? TPS) microcapsules ? B. subtilis was significantly increased (P \ 0.05); activities of LSZ, SOD, AKP and C3 content were significantly higher than in other groups (P \ 0.05). The challenge test showed that the cumulative mortality of sea cucumbers fed a diet supplemented with (APS ? TPS) microcapsules ? B. subtilis reduced significantly (P \ 0.05). In conclusion, dietary combinations of (APS ? TPS) microcapsules ? B. subtilis has a potential for use in diet formulations for sea cucumbers to significantly increase growth, immunity and disease resistance against V. splendidus infection.