Abstract: The yellow cattle were artificially infected with FMDV O/Akesu/58 strain to develop the carrier state. To reveal antigenic variation of FMDV persistent infection isolates, the isolates and serum were obtained monthly to study the antigenicity of the isolates and the neutralization characteristic of serum and antibody level. By RT-PCR, the VP1 gene of the isolates were amplified and the variation of antigenic gene were analysized during FMDV persistent infection. The neutralization activity of the isolates and themselves serum were tested by microserum virus neutralization assay and the antibody titre to structural protein were detected with liquid-phase blocking ELISA. At the same time, the relationship of them was analyzed. The results showed that the homology of VP1 nucleotide sequence of all the isolates was above 98%, no base deletion or insertion was found. Compared with O/Akesu/58 strain, the homology of VP1 nucleotides sequence of the isolates was 85%, amino acid sequences only being 90%.The VP1 gene of the isolates had several nucleotides mutations, including 16 coincident nucleotides mutations compared with their parental strain, only two point mutation leading to amino acid change(I56→T,A210→E),and there were 4 transversion mutations and 3 amino acid among the isolates. Moreover, it was found that the different time isolates and the corresponding serum could counteract and the neutralization activity were gradually declined with higher neutralizing activity, the lowest was 1∶80.The results were coincident with the detection of Liquid phase blocked-ELISA. These results illuminated，during the yellow cattle persistently infected FMDV, antigenic variation of the isolates were unremarkable and could be recognised by themselves cattle serum, moreover the serum and the isolates could specially counteract with high neutralizing antibody titre. But the relativity of serum antibody titre and obtaining isolates was vague.