Peroxiredoxin II (PrxII) is one of reactive oxygen species (ROS)-degrading enzyme. Here, we investigated the role of PrxII on toll-like receptor 4 (TLR4) and B-cell activating factor (BAFF) expression in ovalbumin (OVA)-induced mouse asthma. We used ROS-producing PrxII−/− mice of which cells up-regulate BAFF expression. As significant changes were detected in TLR4 mRNA with real-time quantitative RT-PCR analysis, TLR4 protein was decreased in PrxII−/− mouse splenocytes and peritoneal macrophages, compared to wild type cells. Airway hyper-responsiveness (AHR) was more severe in PrxII−/− mice than wild type mice, which was measured by the level of various parameters, number of eosinophils, IgE level, airway thickness, and mucous secretion. BAFF was detected in cells surrounding airways of OVA-induced mouse and it was highly augmented in PrxII−/− mice. BAFF promoter activity was also higher in PrxII−/− mouse embryonic fibroblast (MEF) than in wild type MEF. Collectively, results show that PrxII may have benefits in asthma through reducing ROS. It suggests that BAFF and TLR4 expressions are differentially regulated by PrxII and TLR4 protein level may not be crucial in OVA-induced asthma.