Abstract: Vibrio harveyi, a main pathogen of maricultured fish, causes great economic loss in aquaculture industry. We tested the temporal and spatial distribution of drug resistance of 90 V. harveyi strains isolated from maricultured fish in the South China Sea by Kirby-bauer diffusion method. Phylogenetic of drug resistance was analyzed by squared Euclidean distance using bacteriostatic rings diameter of 12 kinds of antibiotics. The diversity of the drug resistance spectrum of 90 strains was also discussed. Results show that 90 V. harveyi strains formed 26 antibiogram types and antibiogram abundance was 28.9%. Thirty-five strains, occuping 38.9% of total strains, had 21 multi-drug antibiogram types (resistant to ≥ 3 antibiotics), which was 80.8% of spectral richness. The antibiogram types show significant difference of 90 V. harveyi strains in years and regions: 10, 18 and 8 in 2012, 2013 and 2014 years, respectively, while 17, 13 and 2 kinds in Hainan, Guangdong and Guangxi Provinces correspondently. Phylogenetic and cluster analysis indicate that 90 strains separated to Group Ⅰ, Group Ⅱ and others clusters. Eleven antibiogram types with abundance of 16.9% in Group Ⅰ, and 12 antibiogram types with 57.1% in Group Ⅱ, while four kinds with 100% in other clusters. Group Ⅰ and Group Ⅱ could be divided into five subgroups of ⅰ~ⅴ. The results indicate that V. harveyi strains display complex antibiogram types in Hainan, Guangdong and Guangxi Provinces, and the resistance spectrum of V. harveyi changes and expands as time goes on.