Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2025 12 05 1 9 Wenru Wu School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China Lei Yang School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China Binbin Fu Department of Otolaryngology, The Third People's Hospital of Deqing County, Deqing, HuZhou, Zhejiang, China Huiyang Lv Department of Otolaryngology, Zhejiang Hospital, Hangzhou, Zhejiang, China Honglin Wu Department of Otolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China 2025 03 26 2025 07 25 Allergic rhinitis (AR), as a chronic disease, seriously affects the quality of life of patients while concurrently exerting a significant economic and healthcare burden on the medical system. However, the existing treatment methods have certain limitations, and more effective treatment strategies are needed. To this end, we proposed an ovalbumin-induced guinea pig model of AR to investigate the potential impact of activated polyethylene glycol (PEG) with varying molecular weights and concentrations in local nasal treatment. The therapeutic effect was evaluated by behavioral score, serological detection, and histopathological observation. The behavioral assessment demonstrated significant alleviation of sneezing frequency, nasal pruritus, and clear nasal discharge in the activated PEG-600 treatment groups relative to the sham group. However, statistical analysis revealed no appreciable intergroup differences between the activated PEG-3400 treatment groups and the sham group. Histopathological evaluation disclosed a marked reduction in eosinophilic infiltration in the activated PEG-600 group, accompanied by preservation of nasal mucosal structural integrity and notable attenuation of inflammatory infiltration. In contrast, the activated PEG-3400 group exhibited comparatively limited therapeutic efficacy, demonstrating only a subtle reduction in inflammatory cell counts and more pronounced disorganization of mucosal epithelial architecture compared to the PEG-600-treated group. Serum immunological profiling indicated that while local inflammatory markers showed evidence of mitigation, systemic immune parameters remained unaffected by either activated PEG formulation. These findings underscore the differential efficacy profile between PEG-600 and PEG-3400 derivatives in ameliorating AR symptoms, among which PEG-600 exhibits superior anti-inflammatory effects. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4396 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4396/2269