Despite the growing interest in the molecular epidemiology of pestivirus, there have been few attempts to determine which regions of the pestivirus genome are subject to positive selection, although this may be a key indicator of the nature of the interaction between host and virus. By using likelihood-based methods for phylogenetic inference, the positive selection pressure of BVDV-1 E2 gene were assessed and a site-by-site analysis of the dN/dS ratio was performed, to identify specific codons undergoing diversifying positive selection. The overall omega was 0.20, indicating that most sites were subject to strong purifying selection and five positively selected sites (886, 888, 905, 944, and 946) were identified. It is surprising to find that all the potential positively selected sites fall within the C-terminal of E2, and out of the N-terminal of E2 which is thought to be surface-exposed and therefore prime targets for host antibody response. In conclusion, these results suggest that selection favoring avoidance of antibody recognition has not been a major factor in the history of BVDV-1. Further analysis is necessary to see if amino acid substitutions in the BVDV-1 positively selected sites can lead to change of host tropism or\and escape from epitope-specific CD8 T-cell response.