Abstract: The antibacterial effects of drugs on Pseudomonas plecoglossicida in vitro and effects of the drugs on disease resistance of orange spotted grouper, Epinephelus coioides, were studied in order to screen traditional Chinese herbal formula and Chinese and Western medicine combination formula for effective treatment of Pseudomonas plecoglossicida diseases of the grouper. Based on the bacteriostatic test of traditional Chinese medicine formula against P. plecoglossicida in vitro, the ratios of Astragalus radix, Coptis chinensis and Cortes phellodendri of Chinese herbal formulas I, II and III are set as 0.9∶1.3∶0.9, 1.2∶0.9∶1.0 and 1.0∶1.0∶1.0, respectively. The ratios of Astragalus radix, Coptis chinensis, Cortes phellodendri and enrofloxaci were different in Chinese and Western medicine combination formulas IV, V and VI, which were added to feed as trial groups. The groups with 3 replicates per treatment of food containing the drug additives at mass fraction of 2.2% were fed to the grouper. The results showed that the Chinese herbal formula III in aqueous solution of 60 mg/mL was the best formula. The mortality in 40 days in the treatments was found in order of control group II > control group IV > control group Ⅲ> trial groupⅠ> trial group III > trial group II > trial group V > trial group VI > trial group IV > control group I. It showed that the Chinese herbal formula II and the combination formula IV were the best formulas for fish disease treatment. Moreover, the combination formula is better than the Chinese herbal formula. Thus, the screened formulas can have better effects on the Pseudomonas plecoglossicida diseases of the grouper.