An effective vaccine against Edwardsiella tarda has not been reported, one of main reasons is the variation in its serotypes. This study aimed to develop an effective vaccine against different serotypes of E. tarda. A conserved 37kDa outer membrane protein (OMP) of E. tarda was obtained by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). It showed comprising several proteins by two-dimensional (2D) PAGE analysis and showed a high similarity to glyceraldehyde-3-phosphate dehydrogenase by N-terminal amino acid sequence analysis. Japanese flounder (Paralichthys olivaceus) vaccinated with the 37kDa OMP was significantly protected against the infections by different serotypes of E. tarda. A specific antibody was also detected by using ELISA. This study suggests that the 37kDa OMP is an effective potent vaccine candidate against different serotypes of E. tarda.