Preeclampsia (PE) affects between 3-8% of all pregnancies worldwide, with life threatening consequences for the fetus and mother, and long-term health implications for the neonate. PE is characterised by an imbalance of placental growth factors, increased soluble fms-like tyrosine kinase-1 (sFlt-1), proteinuria and increased blood pressure. Impaired maternal vascular adaptations to pregnancy are also a common feature of PE. The peptide hormone relaxin mediates renal and uterine haemodynamic adaptations to pregnancy. Low circulating relaxin levels in pregnant women are correlated with maternal vascular dysfunction. Rats and mice deficient in relaxin also have systemic vascular dysfunction, impaired uterine artery remodelling and restricted fetal growth in late pregnancy. However little is known about the effects of relaxin deficiency on the development of other preeclampsia-like symptoms. This study in aged (7 month) relaxin gene knockout (Rln-/-) mice tested the hypothesis that relaxin deficiency affects placental growth factor expression, and increases circulating sFlt and urine protein concentrations on days 12.5 and 17.5 pregnancy. Although there were significant (P < 0.05) differences in VEGF, PlGF and activin A gene expression between the placental regions (labyrinth and decidua basalis), there were no differences between Rln-/- and wildtype Rln+/+ mice. Furthermore, there was no significant difference in plasma sFlt-1 concentrations between the genotypes. Water intake and urine production both increased significantly in Rln+/+ and Rln-/- mice on day 17.5 pregnancy, and there was a significant increase in the albumin: creatinine ratio in the urine of Rln-/- mice on day 12.5 pregnancy but not late pregnancy compared to Rln+/+ mice. These findings suggest that relaxin deficiency exacerbates PE by disrupting normal renal function (leading to proteinuria) rather than causing placenta dysfunction and release of sFlt.