Plant peroxidases (PODs) have been shown to reduce hydrogen peroxide (H2O2) in the presence of an electron donor. Extracellular POD also induce H2O2 production, and can perform a significant function in responses to environmental stresses. We previously described the isolation of 10 POD cDNA clones from cell cultures of sweetpotato (Ipomoea batatas). Among them, the expression of the swpa4 gene was profoundly induced by a variety of stresses. In this study, transgenic tobacco (Nicotiana tabacum) plants overexpressing the swpa4 gene under the control of the CaMV 35S promoter were generated in order to assess the function of swpa4. Both transient expression analysis with the swpa4-GFP fusion protein and POD activity assays in the apoplastic washing fluid revealed that the swpa4 protein is secreted into the apoplastic space. The transgenic plants also evidenced a significantly enhanced tolerance to a variety of abiotic and biotic stresses. These plants harbored increased lignin and phenolic content, and H2O2 was also generated under normal conditions. Furthermore, they manifested increased expression levels of a variety of apoplastic acidic pathogenesis-related (PR) genes following enhanced H2O2 production. These results suggest that the expression of swpa4 in the apoplastic space functions as a positive defense signal in the H2O2-regulated stress response signaling pathway.