Abstract: Objective: To investigate the protective effect of sauchinone (Sch) on apoptosis and oxidative stress of pancreatic β-cells in Streptozocin (STZ)-induced diabetic mice and its relevant mechanisms. Methods: Among 50 male BALB/C mice, 8 mice were randomly selected and grouped to be the normal control group, and the other mice were intraperitoneally received 40 mg/kg STZ. After the confirmation of the onset of diabetes mellitus in 32 mice by measuring the fasting blood glucose level (FBGL), the mice were evenly divided into the model group, low-dose Sch group, high-dose Sch group and metformin-treated positive control group. And the mice in low-dose Sch group and high-dose Sch group were respectively gavaged with 10 or 30 mg/kg Sch, and the mice in metformin-treated positive control group were gavaged with 100 mg/kg metformin once a day for 4 weeks, while the mice in the normal control group and the model group were gavaged with the same volume of saline. During the treatment period, the body weight of each mouse was weekly checked, and at 12 h after the last dosing, the FBGL, the serum insulin concentration, the homeostasis model assessment insulin resistance (HOMA-IR), the serum TNF-α and IL-6 levels were determined. The malondialdehyde (MDA) concentration, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in pancreatic tissues were measured. Moreover, the pancreatic protein expressions of Bcl-2, Caspase-3 and NF-κB were detected by Western blot. Results: Compared with the model group, the body weights in the high-dose Sch groups checked on the 3^rd and 4^th week were significantly increased (P<0.05). The FBGL and the serum insulin concentration in Sch-treated groups rose significantly in a dose-dependent manner (P<0.05). The HOMA-IR was significantly decreased (P<0.05). The levels of TNF-α and IL-6 in serum were significantly decreased (P<0.05). The MDA concentrations in the Sch-treated pancreatic tissues decreased, while the SOD and GSH-Px activities increased significantly in a dose-dependent manner (P<0.05). Additionally, the Sch treatments significantly raised the pancreatic Bcl-2 protein expression while lowed the pancreatic Caspase-3 and NF-κB protein expressions in a dose-dependent manner compared with the model group (P<0.05). Conclusions: Sch protects diabetic mice islet β cells, and the mechanism may be mediated by its anti-inflammation and anti-oxidative stress as well as anti-apoptosis actions.