Objective:To observe the effect of mulberry leaf extract on blood glucose and islet β cell proliferation in pregnant diabetic rats.Methods:The rat model of gestational diabetes mellitus was prepared. The 32 model rats were randomly divided into the model group, metformin group, low dose mulberry leaf extract group and high dose mulberry leaf extract group, 8 rats in each group. Eight normal pregnant mice were selected as the control group. The low and high dose groups received gavage of mulberry leaf extract 0.5 and 1.5 g/kg, respectively, the rats in the metformin group received gavage of 200 mg/kg metformin hydrochloride suspension, and the model group and the normal group received gavage of sterile normal saline of equal volume. The intervention continued for 4 weeks. The HE staining was used to observe rat pancreatic tissue pathology change. The fasting blood glucose level was measured by blood glucose meter. The TC, TG, LDL-C and HDL-C levels were measured by automatic biochemical detector. The fasting insulin level was measured by enzyme-linked immunosorbent assay, and the islet resistance index and insulin sensitivity index were calculated. The activity of SOD, CAT, GSH-pX and MDA level in serum were detected by radioimmunoassay. The MTT method was used to detect islet β cell proliferation, and the Western blot method was used to detect CDK4, pRB, E2F1 protein expression.Results:Compared with the model group, the low-dose and high-dose groups showed that the levels of FBG, TC, TG and LDL-C significantly decreased ( P<0.05), and the HDL-C levels significantly increased ( P<0.05). Compared with the model group, the low-dose and high-dose groups showed that fasting insulin and islet resistance index significantly decreased ( P<0.05), and insulin sensitivity index significantly increased ( P<0.05). Compared with the model group, the low-dose and high-dose groups showed that the levels of SOD (360.62 ± 27.96 U/ml, 401.62 ± 25.66 U/ml vs. 293.45 ± 31.36 U/ml), CAT (10.26 ± 2.07 U/ml, 12.26 ± 0.96 U/ml vs. 8.26 ± 2.44 U/ml), GSH-Px (790.23 ± 47.87 U/ml, 880.63 ± 40.62 U/ml vs. 716.62 ± 45.62 U/ml) significantly increased ( P<0.05), MDA (30.89 ± 3.28 mmol/ml, 40.42 ± 2.06 mmol/ml vs. 44.85 ± 5.33 mmol/ml) level significantly decreased ( P<0.05). After 48 h and 72 h of modeling, compared with the model group, the islet proliferation rate of the low-dose group and the high-dose group significantly increased ( P<0.01). Compared with the model group, the low-dose and high-dose groups showed that the CDK4 (1.15 ± 0.42, 1.35 ± 0.59 vs. 0.75 ± 0.22), pRB (1.11 ± 0.58, 1.54 ± 0.64 vs. 0.67± 0.20), E2F1 (1.06 ± 0.39, 1.27 ± 0.18 vs. 0.48 ± 0.12) protein expression significantly increased ( P<0.05). Conclusions:Mulberry leaf extract can effectively improve blood sugar, lipid and insulin levels in gestational diabetic rats, and promote the proliferation of pancreatic beta cells by regulating CDK4-pRB-E2F1 pathway-related proteins.