To investigate the effects of beraprost sodium on the proliferation and oxidative stress of glomerular mesangial cells under high glucose conditions, a rat mesangial cell line (rat mesangial cells; RMCs) was treated with beraprost sodium in the presence of high glucose concentrations. Proliferation rates of mesangial cells were detected by MTT assays and BrdU incorporation analyses. Levels of reactive oxygen species (ROS) were detected by DCFH-DA probes. The mRNA expression levels of CuZnSOD, MnSOD, catalase (CAT), glutathione peroxidase (Gpx), and collagen IV were detected by RT-PCR, and the protein levels of antioxidants (i.e. CuZnSOD, CAT, and MnSOD) and collagen IV were detected by Western blot. Beraprost sodium treatment significantly decreased the proliferation and ROS levels of RMCs cultured in high glucose conditions in a dose-dependent manner (p < 0.05). Beraprost sodium treatment decreased the mRNA and protein levels of CuZnSOD, CAT, and collagen IV in cells under high glucose conditions, while it increased MnSOD protein levels in cells under normal glucose conditions. Therefore, beraprost sodium inhibits high glucose-induced cellular proliferation and the generation of ROS, and it improves the antioxidant capacities of rat glomerular mesangial cells.