The optimization of aqauculture on Eleutheronema tetradactylum avoids Food safety hazard of drug is urgent need. Here, we designed that the diffrent quantities of diet and stocking densities to probe the optimal aquaculture model of Eleutheronema tetradactylum. There was using Bacillus subtilis, B. amyloliquefaciens, and Bacillus sp. on aquaculture and then inspected the effect of water qaulity parameters (total ammonia, NO2, NO3, and Vibrio spp.), and also investigated the relevancy of meteorological parameters (temperature, atmospheric pressure, and relative humidity) and water qaulity parameters (total ammonia, NO2, NO3, and total plate count). The results showed that the optimal feeding diets were 3% body-weight/day, the optimal stocking densities were 7 to 10 fish/m2 . There were little relevancy of meteorological parameters and water qaulity parameters (R2 =0.53). B. subtilis had Better effect on water quality, and B. amyloliquefaciens had Better effect on inhibition of Vibrio spp.. We could use the probiotics according to the situation on aquaculture of Eleutheronema tetradactylum.