Ginsenoside Rh1 is able to upregulate glucocorticoid receptor (GR) level, suggesting Rh1 may improve glucocorticoid efficacy in hormone-dependent diseases. Therefore, we investigated whether Rh1 could enhance the effect of dexamethasone (Dex) in the treatment of MRL/lpr mice. MRL/lpr mice were treated with vehicle, Dex, Rh1, or Dex + Rh1 for 4 weeks. Dex significantly reduced the proteinuria and anti-dsDNA and anti-ANA autoantibodies. The levels of proteinuria and anti-dsDNA and anti-ANA autoantibodies were further decreased in Dex + Rh1 group. Dex, Rh1, or Dex + Rh1 did not alter the proportion of CD4+ splenic lymphocytes, whereas the proportion of CD8+ splenic lymphocytes was significantly increased in Dex and Dex + Rh1 groups. Dex + Rh1 significantly decreased the ratio of CD4+/CD8+ splenic lymphocytes compared with control. Con A-induced CD4+ splenic lymphocytes proliferation was increased in Dex-treated mice and was inhibited in Dex + Rh1-treated mice. Th1 cytokine IFN-γ mRNA was suppressed and Th2 cytokine IL-4 mRNA was increased by Dex. The effect of Dex on IFN-γ and IL-4 mRNA was enhanced by Rh1. In conclusion, our data suggest that Rh1 may enhance the effect of Dex in the treatment of MRL/lpr mice through regulating CD4+ T cells activation and Th1/Th2 balance.