Objective: This study aims to investigate the antioxidant properties and protective effects of Heracleum persicum (HP) extract in streptozotocin (STZ)-induced diabetic rats. Material and Methods: Forty-two Wistar albino male rats were divided into six groups including Control (C); Diabetes mellitus (DM); DM+Akarboz 20 mg/kg; DM+100 mg/kg HP extract (HP1); DM+200 mg/kg HP extract (HP2) and DM+400 mg/kg HP extract (HP3). Experimental diabetes was established by a single-dose [45 mg/kg, intra-peritoneal (i.p)] STZ injection. Essential dosages of HP extracts and Akarboz were applied with gastric gavage for 21 day. Results: In histopathological evaluation of the stained liver and kidney sections of diabetic rats showed degeneration and necrosis of hepatocytes, inflammatory cell infiltration and hydropic degeneration and necrosis in tubulus epithelial cells, disorder of glomerular structure and lymphocyte infiltration. These histopathological changes were ameliorated in the HP-treated rats depending on the dose level. Glutathione peroxidase 1 (GPx-1) immunoreactivity was detected in hepatocytes of liver and tubule epithelial cells of kidney. We have shown that treatment with extracts of HP modulates GPx-1 expression in HP-treated rats. STZ-induced degenerative changes in beta-cells caused decreases in the number of functioning beta-cells and insulin immunoreactivity in the pancreas of the diabetic rats. The pancreas of HP-treated rats were improved and the number of immunoreactive beta cells were significantly increased. Conclusion: Our data suggests that the STZ-induced immunohistochemical and histopathological alterations could be prevented by HP extract probably due to possess the ability to regenerate beta-cells.