ObjectiveExploring the potential causal effects and directions of insulin resistance (IR) and chronic airway inflammatory diseases, including asthma and chronic obstructive pulmonary disease (COPD), through two sample Mendelian randomization (MR). MethodsA total of 53 validated single nucleotide polymorphisms (SNPs) associated with IR were selected as instrumental variables. The inverse variance-weighted (IVW) method was used to model the causal association, and sensitivity analyses through leave-one-out analysis and pleiotropy testing were conducted to assess the relationship between IR and asthma and COPD. ResultsMR analysis revealed no significant causal effect of IR on asthma (IVW: OR=1.067, 95%CI 0.871 to 1.306, P=0.531) or COPD (IVW: OR=0.906, 95%CI 0.686 to –1.196, P=0.557). The results were consistent across sensitivity analyses and multiple pleiotropy tests, with no evidence of horizontal pleiotropy detected. ConclusionNo causal association was found between IR and the development of asthma or COPD. The relationship between these conditions may be influenced indirectly through complex interactions between metabolic and inflammatory pathways affecting disease progression.