Pseudomonas plecoglossicida is the causative agent of visceral granulomas disease (VGD) in large yellow croaker (LYC, Larimichthys crocea) farming. However, multi-antibiotic resistant of P. plecoglossicida creates an urgent need of an efficient vaccine to combat this pathogen. In this study, an inactivated vaccine added polyactin (PA), CpG-riched plasmid (pCpG) and aluminum adjuvant (Al) was developed. As a result, its relative percentage survival (RPS) against P. plecoglossicida were up to 64%. Comparatively, RPS of groups that vaccinated with vaccines adjuvanted with PA and Al or CpG and Al were 49% and 39%. However, an interesting result that the vaccine combined with PA, CpG and Al did not show the strongest activation of total serum protein and antibody levels in serum among three vaccinated groups. According to expressions of some cellular immune related genes, we found that the inactivated vaccine combined with PA, CpG and Al was more likely to induce a cellular immune response rather than humoral immune response. Totally, our study demonstrated that the mixture of PA, CpG and aluminum adjuvant is a potential adjuvant system for LYC vaccine development.