The treatment of allergic diseases, such as asthma, with both conventional and novel therapies presents a challenge both in terms of optimal effect and cost. On the other hand, traditional therapies utilizing natural products such as onion have been in use for centuries with demonstrated efficacy and safety but without much knowledge of their mechanims of action. In this study, we investigated if the anti-inflammatory effects of onion bulb extract (OBE) are mediated via the modulation of the EGFR/ERK1/2/AKT signaling pathway, and whether OBE can synergise with steroids to produce greater anti-inflammatory actions. Treatment with OBE inhibited the house dust mite (HDM)-induced increased phosphorylation of EGFR, ERK1/2 and AKT which resulted in the inhibition of HDM-induced increase in airway cellular influx, perivascular and peribronchial inflammation, goblet cell hyper/metaplasia, and also inhibited ex vivo eosinophil chemotaxis. Moreover, treatment with a combination of a low dose OBE and low dose dexamethasone resulted in a significant inhibition of the HDM-induced cellular influx, perivascular and peribronchial inflammation, goblet cell hyper/metaplasia, and increased the pERK1/2 levels, whereas neither treatment, when given alone, had any discernible effects. This study therefore shows that inhibition of the EGFR/ERK1/2/AKT-dependent signaling pathway is one of the key mechanisms by which OBE can mediate its anti-inflammatory effects in diseases such as asthma. Importantly, this study also demonstrates that combining OBE with steroids results in significantly enhanced anti-inflammatory effects. This action may have important potential implications for future asthma therapy.Keywords:asthma; onion (Allium cepa Hysam); signalling; steroids; synergisctic effects.