Introduction: Maternal obesity and diabetes are increasingly prevalent during pregnancy and may have long-term consequences on the offspring’s health. Previous work has suggested that in mice a maternal high fat diet can produce an insulin resistant phenotype in the mother and reduce placental expression of specific amino acid transporter genes and circadian clock genes. Metformin is an antidiabetic drug that improves the glycaemic control. This study aims to determine whether metformin treatment during pregnancy can modify the effect of a maternal high fat diet on placental expression of amino acid transporter and circadian clock genes in the mouse.Methods: Female C57BL6 mice (n=22) were exposed to the independent variables ‘diet’ (control diet, 7%kcal fat or high-fat diet, 45% kcal fat) for 6 weeks before conception and during pregnancy, and ‘treatment’ (control treatment, no metformin or treatment, metformin in drinking water at 250mg/kg/day) during pregnancy. Pregnant dams were killed by cervical dislocation on day 16 of pregnancy (pregnancy period in mice is 21 days) and their placentas were collected, snap frozen and stored at -80°C. These placentas came from 4-5 litters/group (2-3 placentas per dam): control diet with control treatment (CC, n=12), control diet with metformin treatment (Cm, n=15), high-fat diet with control treatment (HFC, n=18), and high-fat diet with metformin treatment (HFm) (n=21). Expression levels of the circadian clock genes Clock, Bmal, Per2 and Cry2, and amino acid transporter genes Snat2, Tat1 and Lat1, were measured by quantitative real-time PCR. Data were analysed using two-way ANOVA.Results: Maternal high fat feeding reduced the placental mRNA expression of Snat2 (p<0.001) and Tat1 (p=0.037). Metformin treatment reduced the expression of placental Tat1 (p< 0.001). There was an interaction between maternal diet and metformin treatment for Lat2, with reduced expression in placentas from dams on control diet and given metformin, and increased placental expression in high fat fed dams on metformin (p=0.006). Expression of the circadian clock genes Clock and Per2 were lower in metformin treated dams, and there was an interaction between maternal diet and metformin treatment for Clock (p=0.031). Conclusions: Our results show that both maternal high fat diet and metformin treatment during pregnancy are associated with changes in placental gene expression. However metformin treatment did not reverse changes in gene expression as a result of feeding pregnant dams with a high fat diet, suggesting that their effects are mediated by different pathways. Further work is required to identify these pathways.