This study aimed to evaluate the antimicrobial effects of the medicinal plant Ecballium elaterium, which is topically applied as a traditional medicine for the treatment of rhinosinusitis. Pure and extract forms of E elaterium were applied to the nasal cavity of rats for the treatment of Streptococcus-pneumoniae -induced rhinosinusitis. The nasal mucosa, soft palate, and trachea of the rats were harvested in the first hour, third day, and third week for histopathologic evaluation. This experiment revealed the anti-inflammatory effects of E elaterium and showed that it reduced fibrosis. The anti-inflammatory effect of all forms of E elaterium was found to reach its maximum level on the third day, decreasing by the third week. We also observed that the pure form of E elaterium caused severe epithelium loss in the first hour after application. The mechanism of the anti-inflammatory effect of different levels of extract forms needs to be further analyzed with different doses and duration of treatment.