Background <p>Pre-eclampsia is a significant contributor to maternal and neonatal morbidity and mortality. However, its etiology remains elusive. More and more studies have highlighted the potential involvement of folic acid metabolism in the development of pre-eclampsia. Folic acid is known to be important for DNA synthesis and methylation processes, which are crucial during pregnancy. Disruptions in these pathways may contribute to the pathogenesis of pre-eclampsia. Clinical studies investigating associations between folic acid supplementation and pre-eclampsia produced inconsistent results. The research aims to explore the potential link between folic acid deficiency and the development of pre-eclampsia-like symptoms in rat models, shedding light on the possible role of one-carbon metabolic pathways in the etiology of pre-eclampsia.</p> Methods <p>Establishing a rat model with severe and moderate folate deficiency by providing female rats with a folate-deficient diet from birth or weaning, respectively. The effects on folate and homocysteine levels during pregnancy were then studied.</p> Results <p>Both groups exposed to folate deficiency exhibited decreased levels of 5-methyltetrahydrofolic acid in both plasma and red blood cells, along with increased levels of homocysteine in plasma, compared to the control group. Consistent high blood pressure and urinary protein excretion were not significantly different among the three groups. However, fetuses from the folate-deficient group exhibited noticeably lower body weight compared to those from the folate-replete group.</p> Conclusions <p>Folate deficiency alone may not be sufficient to cause pre-eclampsia in rats, but it does increase the risk of offspring being small for their gestational age at birth.</p>