A flavivirus, named duck tembusu virus (DTMUV), emerged in China in 2010. This virus has caused great economic losses in the poultry industry in China and may pose a threat to public health. As a safe, efficient and convenient vaccine development strategy, DNA-based vaccines have become a popular approach for both human and veterinary applications. Attenuated bacteria have been widely used as vehicles to deliver heterologous antigens to the immune system. Thus, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-SME) based on envelope proteins (prM and E) of DTMUV and attenuated Salmonella typhimurium aroA- strain SL7207 was developed and evaluated in this study. The prM and E antigen proteins were successfully expressed from the vaccine SL7207 (pVAX1-SME) both in vitro and in vivo. High titers of the specific antibody against the DTMUV-E protein and the neutralizing antibody against the DTMUV virus were both detected after vaccination with SL7207 (pVAX1-SME). Ducks orally vaccinated with the SL7207 (pVAX-SME) vaccine were efficiently protected from lethal DTMUV infection in this study. Taken together, we demonstrated that prM and E proteins of DTMUV possess strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-SME) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large-scale clinical use.