The present study aimed to investigate the role of microRNA‐146a and its adapter proteins [interleukin‐1 receptor‐associated kinase 1 (IRAK1) and tumor necrosis factor (TNF) receptor‐associated factor 6 (TRAF6)] in the pathogenesis of ovalbumin (OVA)‐sensitized rats in association with the diet‐induced obesity condition. Twenty male Wistar rats were divided into four groups: control with normal diet (ND), OVA‐sensitized with normal diet (S + ND), high‐fat diet (HFD), and OVA‐sensitized with high‐fat diet (S + HFD). All the animals were fed for 8 weeks with standard pelts or high‐fat diet, and were then sensitized and challenged with OVA or saline for another 4 weeks. The tracheal responsiveness to methacholine, serum protein levels, and lipid profile levels was measured by the ELISA method. Moreover, the gene expression level of microRNA‐146a (miR‐146a) was measured in the lung tissue of the rats using the real‐time PCR method. Maximum response to methacholin increased in the S + HFD group in compared with ND, S + ND, and HFD groups (P < 0.05 to P < 0.001). Moreover, in the S + HFD group the mRNA expression levels of miRNA‐146a increased in the lung tissue (P < 0.001). In addition, the protein analysis results showed that IRAK1, TRAF6, NF‐kB, and IL‐1β protein levels were high in the S + HFD group compared to the ND and HFD groups; however, in compared with the S + ND group, only the IL‐1β protein level was higher in the S + HFD group (P < 0.05). These results suggest that a defect in the NF‐kB–miR‐146a negative feedback loop may be involved in the pathogenesis of obesity associated with OVA‐sensitized condition. © 2018 BioFactors, 45(1):75–84, 2019