The aim of the study was to investigate the immune effect of fusion protein VP4-STI. 40 mouse were randomly divided into 4 groups of test bacterin group (30 μg VP4-STI +0.6 μg LTB), aluminiumhydroxide vaccine group (30 μg VP4-STI +Al(OH)3 gel ) , pure protein VP4- STI vaccine group (30μg VP4-STI ) and PBS control group were immunized by rhinal dripping. And then, the antibody levels of the mouse were determined. The protection effects of mouse in all immune groups were observed after the toxicity test with strong virulent strain C83902 of E. coli. Anti-VP4-STI antibodies were produced in other groups with the highest at the 6th week, except PBS control group. The antibody level in aluminiumhydroxide bactetin group was higher than that in test vaccine group. The antibody level in pure protein VP4-STI bacterin group was lower, being extremely significantly different from that in test vaccine group ( P 〈0. 001 ). Mouse in test vaccine group and aluminium hydroxide bacterin group had better immuno-protection effect on strong virulent strain C83902 of E. coli, obviously different from that in PBS control group. The research provided basis for further improving the immunogeneticity of STI.