© 2020, Iranian Journal of Pharmaceutical Research. All rights reserved.Asthma is a disease characterized by spontaneous contraction of the airways in response to a wide variety of endogenous and exogenous stimuli. Many asthma models are used to mimic the human asthma model in the literature. In order to better understand the role of the cannabinoid (CB) 2 receptor in the ovalbumin (OVA)-induced asthma model, a combination of both selective CB2 agonist (AM1241) and antagonist (AM630) was used to improve inflammatory hypersensitivity and edema in rats. In the present study, it was found that OVA decreased body weight (p < 0.05), increased lung weights (p < 0.05), increased diastolic and systolic blood pressure (p < 0.001), and caused irregularity in pulmonary functions (p < 0.001). Moreover, CB2 agonist was found not to reduce body weight, cause blood pressure and respiratory irregularities (p < 0.05). OVA led to increase in IgE, TNF-α, IL-4, MDA level (p < 0.001), and total WBC count (p <.05). CB2 treatment caused to reduce the number of total WBC and the level of total protein in BALF, to hinder to increase level of MDA, IgE, TNF-α, and IL-4 (p < 0.05) in BALF or serum or lung tissue. But CB2-antagonist treatment prevented the protective effect of CB2 agonist. The aim of this study was to study the role of the CB2 receptor in the OVA induced asthma model, to improve inflammatory hypersensitivity, and edema in the rats. The results suggested that CB2 agonist administration to OVA induced asthmatic rats via anti-asthmatic potential through inhibition of parameters such as IgE, IL-4, TNF-α, microvascular escape, and oxidative stress.