<p>This study aimed to investigate the immunostimulatory activities of herbal extract, focusing on <i>Pharbitis nil</i> (L.) Choisy seed (PN) extract, known for its several pharmacological effects in traditional and modern medicine. The immunomodulating effect of PN extract was evaluated in cyclophosphamide (CY)-induced immunosuppression mice. The results revealed that PN extract could directly modulate the immune activity of CY in mice by attenuating its damage to spleen and thymic tissues. PN extract could significantly promote the level of serum cytokines such as IL-4 and IL-10, thus modulating the immune function of immunosuppressed mice possibly by the main mechanism of Th2 type immune response. In addition, PN extract had the effect of enhancing humoral immune response by markedly increasing the level of serum immunoglobulins such as IgM and IgG. Therefore, PN extract may be a potential immunomodulator to ameliorate CY-induced immunosuppression. These findings demonstrate that <i>Pharbitis nil</i> seed extract is a promising immunomodulator that attenuates immunosuppression by selectively enhancing Th2-mediated and humoral immune pathways.</p> Graphical Abstract <p></p>