INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. METHODS:: Rat diabetes was induced by intraperitoneal injection of STZ. The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Serum levels of C-peptide and insulin were analyzed using radioimmunoassay kits. RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo.