Astragalus membranaceus (Fisch) Bge (Huang-Qi) is a well-known herbal medicine with tonic property and has been widely used to treat cancer and other immune disorders in China and Southeast Asia for thousands of years. Accumulating evidence suggests that Huang-Qi possesses both immune-boosting and anti-inflammatory/immune-regulatory effects clinically, leaving the mechanism elusive. Recently, we discovered that Astragaloside (ASI), a major active component of Huang-Qi, is able to increase CD45 phosphatase activity. In this paper, we reviewed the recent progress of ASIs in immunoregulatory and anti-inflammatory activities, including the induction of T-cell activation, regulation of effector/regulatory T-cell balance, enhancement of CD45 phosphatase activity, inhibition of pro-inflammatory cytokine and, NF-[Formula: see text]B pathway. Finally, we hypothesized that inducing interferon-[Formula: see text] (IFN-[Formula: see text]) activity by activating CD45 protein tyrosine phosphatase (PTPase) may be involved in the protective role of ASI in two contrary immune-associated diseases. These pharmacological properties highlight the traditional uses of Astragalus and provide a new direction for subsequent research and the clinical application of this traditional herbal.