A chronic inflammatory response possibly mediated by Amyloid β (Aβ) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1β. IL-1β could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1β by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1β vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1β and IL-1RA have not been clearly defined in the experimental rat model of AD induced by Aβ. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1β ratio in the hippocampus of rats after Aβ treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3β phosphorylation, and thereby contribute to IL-1β release decrease as well as a concurrent increase in the level of IL-1RA through NF-κB and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/ IL-1β balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.