Abstract： The effects of progesterone are mediated by its nuclear or membrane receptors, which have been identified in a variety of immune cells including lymphocytes, natural killer cells, monocytes, etc. Recently, a growing body of evidence has confirmed the immunomodulatory activities of progesterone, including induction of T helper 2 (Th2) cell response, inhibition of Th1 cell reaction, promotion of asymmetric antibody synthesis by B cells, suppression of killing activity of natural killer cells and monocytes, which are mediated directly by its receptors or indirectly by progesterone-induced blocking factors. Lower level of progesterone in sera and impaired progesterone receptor expression have been identified in systemic lupus erythematosus, which may result in an attenuation in the immunomodulatory effect of progesterone, and contribute to the initiation and progression of systemic lupus erythematosus.