To develop a safe, effective, and convenient vaccine for the prevention of highly pathogenic avian influenza (HPAI), we have successfully constructed two recombinant lactobacillus strains (LA4356-pH and DLD17-pH) that express the foreign HPAI virus protein hemagglutinin 1 (HA(1)). The mucosal and systemic immune responses triggered by these two recombinant lactobacilli following oral administration to BALB/c mice were evaluated. The results showed that both LA4356-pH and DLD17-pH could significantly increase the specific anti-HA(1) IgA antibody level in the mucosa and the anti-HA(1) IgG level in serum, as well as stimulating the splenic lymphocyte proliferative reaction through increased expression of interleukin-4 (IL-4). Compared with LA4356-pH, DLD17-pH was more effective at inducing systemic and mucosal immune responses, with higher anti-HA(1)-specific IgA and IgG levels. Therefore, DLD17-pH could be a promising oral vaccine candidate against HPAI.