Background: Peroxisome proliferator-activated receptors were reported to regulate inflammatory responses in many cells. In this study we examined the effect of intranasal rosiglitazone on airway smooth muscle thickening in chronic asthma model. Method: We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitised mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with rosiglitazone during OVA challenge. Result: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and features of airway remodeling. Administration of rosiglitazone intranasally significantly inhibited the development of eosinophilic inflammation and airway smooth muscle remodeling in mice chronically exposed to OVA. The expression of TLR-4 and NF-kB were increased in OVA group and decreased in rosiglitazone group. Treatment of GW9660 (rosiglitazone antagonist) decreased expression of TLR-4 and NF-kB. The level of PGE2 was elevated in OVA group and decreased in rosiglitazone group. Treatment of GW9660 decreased the level of PGE2. Conclusion: These results suggest that intranasal administration of rosiglitazone can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4, NF-kB, and PGE2 pathways.