Zingansikpoongtang (ZST) is a Korean herbal prescription, which has been successfully applied for the various neurodegenerative diseases. However, its effect remains unknown in the experimental models. In this study, we examined the effect of ZST on production of interleukin (IL)-6 and IL-8, and expression of cyclooxygenase (COX)-2 in IL-1beta and beta-amyloid [25-35] fragment (Abeta)-stimulated human astrocytoma cell line U373MG. We examined the biological effects of ZST in U373MG cells using MTT assay, enzyme-linked immunosorbent assay, and Western blotting. ZST alone had no effect on the cell viability. The production of IL-6 and IL-8 was dose-dependently inhibited by pretreatment with ZST (0.01-1 mg/ml) on IL-1beta and Abeta-stimulated U373MG cells. The expression level of COX-2 protein was up-regulated by IL-1beta and Abeta, but the increased level of COX-2 was partially down-regulated by pretreatment with ZST (1 mg/ml). These data indicate that ZST has a modulatory effect of cytokine production and COX-2 expression on IL-1beta and Abeta-stimulated U373MG cells, which might explain its beneficial effect in the treatment of various neurodegenerative diseases.