In this study, we attempted to explore the effect and possible mechanism of Andrographolide on OVA-induced asthma. OVA challenge induced significant airway inflammatory cell recruitment and lung histological alterations, which were ameliorated by Andrographolide. The protein levels of cytokines in bron-choalveolar fluid (BALF) and serum were reduced by Andrographolide administration as well as the mRNA levels in lung tissue. Mechanically, Andrographolide markedly hampered the activation of nuclear factor-kappa B (NF-kappa B) and NLRP3 inflammasome both in vivo and vitro thus decreased levels of TNF-alpha and IL-1 beta. Finally, we confirmed that ROS scavenging was responsible for Andrographolide's inactivation of NF-kappa B and NLRP3 inflammasome signaling. Our study here revealed the effect and possible mechanism of Andrographolide on asthma, which may represent a new therapeutic approach for treating this disease.