AIM: To investigate the effect of Bu-Zhong-Yi-Qi-Tang (Decoction for Reinforcing Middle Jiao and Replenishing Qi) on deficiency of N-glycan/nitric oxide (NO) and islet damage induced by injecting two medium doses of streptozotocin (STZ). METHODS: Diabetes was induced by intraperitoneal injection of STZ at 55 mg/kg on day 1 and day 8. Islet damage was evaluated using a scoring system. Nitrite, nitrate, α-mannosidase and amylase activities were measured by colorimetry. N-glycan patterns of amylase were determined with lectin [ConA, pisum sativum agglutinin (PSA), peanut agglutinin (PNA), and lens culinaris agglutinin (LCA)] affinity precipitation method. RESULTS: Severe islet necrosis and mild islet atrophy were observed in diabetic rats. The number and size of islets, the activities of α-mannosidase, amylase and nitrite were decreased, while the binding of PNA and LCA to amylase was increased. All of which were improved after treatment with Bu-Zhong-Yi-Qi-Tang. Islet damage was significantly correlated with nitrite, nitrate, α-mannosidase, amylase and the binding of LCA, PNA, and PSA to amylase. PNA, and PSA to amylase.CONCLUSION: STZ- induced i s let damage i s related to N-glycan def iciency in proteins by blocking α-mannosidase activity and no deficiency, accumulation of unfolded proteins, and endoplasmic reticulum stress and activation of cellular signals, all of which are improved after treatment with Bu-Zhong-Yi- Qi-Tang.