Objective To investigate the protective effects and mechanism of rosiglitazone on streptozotocin (STZ)-induced diabetic rats. Methods The healthy Wistar rats were fasted for 12 h, then injected peritoneally 60 mg/kg STZ solution to establish type 1 diabetic models and randomly assigned to receive 5 mg/kg rosiglitazone for treatment or not once a day for 30 d (n=10 in each group). Another five normal Wistar rats were injected with citrate buffer solution as normal controls. Plasma glucose concentration and weight of the rats were measured and recorded every three days. Rats were sacrificed on day 31 and 61 after the treatment began respectively. HE immunohistochemical staining were performed to observe the beta cells of pancreatic islet and the expression of nNOS. Results As compared with the untreated group, the diabetic symptoms of the treated rats relieved significantly, and no obvious pathologic changes were observed in pancreatic islets. The amount of beta cells of pancreatic islet increased obviously, and the expression of nNOS was much stronger on day 61. Conclusion Rosiglitazone might play a protective role on the islets of STZ-induced diabetic rats and be helpful for the recovery of pancreatic function by inhibiting the activity of iNOS in macrophages at early phase, promoting the expression of nNOS at the late phase, reducing the inflammation of the pancreatic islets and preventing the pancreatic beta cell from being impaired.