Objective To investigate the effect of apigenin (AP) on the C/ EBP homologous protein (CHOP) signaling pathway in the pancreatic endoplasmic reticulum of GDM rats. Methods Pregnant female SD rats were randomly divided into a normal group, model group (GDM group), AP low (0. 23 g / kg), medium (0. 46 g / kg), high (0. 92 g / kg) dose groups, and insulin-positive group (20 U/ kg), with 10 rats in each group. The GDM model was established by intraperitoneal injection of streptozotocin (STZ, 45 mg / kg) on the day of conception. Except for the normal group, each group was treated on the 5 d of pregnancy, and each AP group was administered the corresponding dose of AP by gavage. The insulin-positive group was administered the corresponding dose of insulin by subcutaneous injection, and the normal and GDM groups were treated with the corresponding dose of normal saline by gavage. Each group was treated once a day for 2 weeks. Twelve hours after the last administration, the fasting blood glucose (FBG) and insulin resistance index (HOMA- IR) were measured using commercially available kits, and hematoxylin and eosin (HE) staining was used to observe the morphological changes of the pancreas. The TUNEL method was used to detect the apoptosis rate of islet cells, and Western blot was performed to detect the relative expression levels of glucose regulatory protein 78 (GRP78) and caspase-12, which are related to the endoplasmic reticulum stress-CHOP pathway in the pancreas. Results Compared with the normal group, the FBG content, HOMA-IR, islet cell apoptosis rate, pancreatic tissue injury, and protein expression of GRP78, caspase- 12, and CHOP were all increased in the GDM group (P< 0. 05). Compared with the GDM group, the FBG content, HOMA-IR, islet cell apoptosis rate, pancreatic tissue injury, and protein levels of GRP78, caspase-12, and CHOP were all significantly decreased in the low, middle, and high dose AP groups and insulin-positive group ( P< 0. 05 ). Furthermore, the above indexes in each AP dose group decreased in a dose-dependent manner, whereas compared with the AP high dose group, there was no significant difference in the above indexes in the insulin-positive group (P> 0. 05). Conclusions AP can inhibit the protein expression of GRP78, CHOP, and caspase-12 in the pancreas of GDM rats, reduce endoplasmic reticulum stress in the pancreas, ameliorate pancreatic injury, and decrease the apoptosis of islet cells in GDM rats.