Salidroside is a biologically active ingredient of Rhodiola rosea, which has several interesting biological properties, including anti-oxidant and anti-inflammatory; however, its anti-allergic effects are poorly understood. The objective of this study is to determine whether salidroside attenuates the inflammatory response in an ovalbumin (OVA)-induced asthma model. OVA-sensitized/challenged mice show airway hyperresponsiveness (AHR) to inhaled methacholine and have an increased amount of T-helper2 type cytokines [interleukin (IL)-4, IL-5, and IL-13] and eosinophils in their bronchoalveolar lavage fluids and lung tissues. However, three successive intraperitoneal administrations of salidroside before the last OVA challenge result in significant inhibition of these asthmatic reactions. Moreover, OVA significantly increases the activation of nuclear factor-kappa B (NFκB) and p38 mitogen–activated protein kinase (MAPK) in lung tissues, whereas salidroside markedly suppresses NF-κB translocation and reduces phosphorylation of p38 MAPK. Furthermore, salidroside attenuates the expression of intercellular adhesion molecule 1 and IL-6 through modulating the activities of p38 MAPK and NF-κB in the BEAS-2B cells stimulated by proinflammatory cytokines. These findings indicate that salidroside protects against OVA-induced airway inflammation and AHR, at least in part via downregulation of NF-κB and p38 MAPK activities. Our data support the utility of salidroside as a potential medicine for the treatment of asthma.