House-Dust-Mites (HDMs) are a major source of indoor aeroallergens for resulted in immune inflammatory disease such as asthma. To evaluate the possible effect of attenuated Escherichia coli (AEC) in a murine model of HDMinduced asthma. Intraperitoneal (100 μL) injection of HDM on day 0 followed by intranasal challenges of 50 μL of HDM significantly induced AHR in Female BALB/c mice (18-20 g). Animals were treated with either ACE (108 CFU/ml) or prednisolone (10 mg/kg) or vehicle on day 0, 7, 14 and 21 immediately before administration of HDM. Various behavioral, biochemical, molecular and histological parameters were assessed. The HDM-induced alteration in lung function test, bronchoalveolar lavage cellular count, and hematological count were significantly restored by AEC treatment. Administration of AEC significantly increased SOD and GSH levels whereas elevated MDA, MPO, and NO levels were decreased significantly by AEC treatment. Elevated levels of serum HDM-specific IgE and IgG1 levels, as well as TNF-α, IL-4, IL-5 and IL-8 levels in lung, were decreased significantly by AEC. However, it failed to produce any significant down-regulation in HDM induced elevated TLR-4 mRNA expression. Administration of AEC reduced lung histological alterations induced by HDM. Thus, findings of present investigation demonstrated that oral administration of attenuated E. coli inhibited HDM-induced AHR via modulation of pro-inflammatory cytokines (TNF-α, IL-4, IL-5, and IL-8), IgE and IgG responses to improved the Th1/Th2 imbalance and attenuated lung injury.