Abstract: Objective: To study the effect of metformin on MEK/ERK pathway and myocardial apoptosis in rats with gestational diabetes mellitus.Methods: The rat model of gestational diabetes mellitus was established.The experimental rats were divided into normal control group, model control group and metformin treatment group, with 12 rats in each group.Metformin treatment group rats were intraperitoneally injected with 70 mg/kg metfor-min every day.ELISA test, hematoxylin-eosin (HE) staining, Tunel, real-time fluorescence quantitative poly-merase chain reaction(RT-qPCR), western blotting and echocardiography were used to detect serum lactate dehy-drogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzyme-MB (CK-MB) levels in serum, superxi-de dismutase (SOD) in myocardial tissue, malondialdehyde (MDA) and nitric oxide (NO) level, heart apoptosis level of muscle tissue, apoptosis-related genes and proteins, cardiac function and myocardial morphology, and the effect of metformin on MEK/ERK pathway in rats in each group.Results: Compared with normal control group, the contents of LDH, cTnI and CK-MB in serum of rats in model control group significantly increased(P< 0.05).Compared with model control group, the contents of LDH, cTnI and CK-MB in serum of metformin treat-ment group significantly decreased (P< 0.05).Metfor-min significantly improved the morphology of rat myo-cardium, reduced the infiltration of inflammatory cells, and improved the degeneration and edema of myocardial cells.Compared with normal control group, the number of apoptotic cells in myocardial tissue of rats in model control group increased significantly.Compared with the model control group, the number of apoptotic cells in the myocardial tissue of rats in metformin treatment group decreased significantly.Compared with normal control group, the levels of Bax/Bcl2, active-caspase 3 and active-caspase 9 in myocardial tissue of rats in model control group significantly increased(P< 0.05).Compared with model control group, the levels of Bax/Bcl2, active-cas-pase 3 and active-caspase 9 significantly decreased in myocardial tissue of rats in metformin treatment group(P< 0.05).The results of echocardiography showed that metformin significantly improved the heart function of rats.Compared with normal control group, the relative protein expressions of P-Mek/MEK, p-ERk1/2/ERK1/2 and SIRT1 in myocardial tissue of rats in model control group significantly decreased (P< 0.05).Compared with model control group, the relative protein expressions of P-Mek/MEK and P-ERk1/2/ERK1/2 in myocardial tis-sue of rats in metformin treatment group significantly increased(P< 0.05).Compared with normal control group, SOD and NO levels in myocardial tissue of rats significantly decreased, while MDA levels significantly increased(P< 0.05).Compared with model control group, metformin significantly increased SOD and NO levels in myo-cardial tissue of rats(P< 0.05), and significantly decreased MDA content(P< 0.05).Conclusion: Metformin can significantly inhibit myocardial damage induced by gestational diabetes mellitus, and its mechanism may be relat-ed to the activation of MEK/ERK signaling pathway.