Outer membrane protein (OMP) is the main member of outer membrane, which is the unique structure of Gramnegative bacterium and plays great role in life function of bacterium. However, few researches were reported about immunogenicity and immunoprotection of outer membrane proteins of Vibrio alginolyticus (Va-OMP). In this paper, we prepared four vaccines about V. alginolyticus (Va) and outer membrane protein of V. alginolyticus. Comparing active and passive immunoprotection of outer membrane protein of V. alginolyticus, 58 kD of outer membrane protein of V. alginolyticus (Va-OMP⁵⁸), inactive V. alginolyticus and lipopolysaccharides of V. alginolyticus (Va-LPS) vaccine, the survival percentage of group Va-OMP and group Va-OMP⁵⁸ was between 62.5%-86.7%. However, the survival percentage of group Va-LPS and group inactive Va was between 50%-62.5%. After being immunized with antiserum and challenged by Va, the survival percentage of group Va-OMP was 53.3% and 66.7%. It showed that Va-OMP vaccine and Va-OMP⁵⁸ vaccine had higher immunogenicity than inactive vaccine and Va-LPS vaccine in mice. Moreover, outer membrane protein (OMP) can induce hypersensitivity reaction in mice by delayedtype hypersensitivity (DTH) test. All the results showed that VaOMP may be the protective antigen which is capable of inducing both humoral immunity and cellmediated immunity (CMI) in mice. The immunoprotection of OMP in Epinephelus fario is in process. The experiment provided the theory base for vaccine preparation of V. alginolyticus. It hopes that Va-OMP⁵⁸ may be the protective antigen of V. alginolyticus and further be a candidate of the subunit vaccine.