Hypoxia and neuroinflammation are key risk factors involved in various pathophysiological neural disorders. Hypoxia can aggravate neuroinflammation and ; however, the underlying mechanisms remain unknown. In the present study, hypoxia [either 3 or 1% oxygen (O)] increased lipopolysaccharide (LPS)-induced expression of the IL-6, IL-1β and TNF-α proinflammatory cytokines in BV2 cells. At the molecular level, both hypoxia and FG-4592, an hypoxia inducible factor 1 pathway activator, effectively induced cyclooxygenase-2 (COX-2) expression. The COX-2 inhibitor celecoxib significantly reduced the expression of cytokines induced by LPS under hypoxic conditions. Additionally, the administration of celecoxib inhibited the activation of microglia as well as cytokine expression in mice administered with hypoxia exposure and LPS injection. The present data demonstrated that COX-2 is involved in the hypoxia-induced aggravation of neuroinflammation stimulated by LPS.