Three different cell models were used;?adipocytes (3T3-L1), hepatocytes (HepG2), and myotubes (C2C12).?These cells were treated with imidacloprid (0, 10, and 20 μM) for 4-6 days followed by treatment with insulin for 15 min to determine responses.?Insulin stimulated glucose uptake was reduced by imidacloprid in all three cell culture models.?Treatment with imidacloprid reduced phosphorylation of protein kinase B (AKT), one of the major regulators of insulin signaling, without changing overall AKT expression.?Subsequently, imidacloprid reduced phosphorylation of ribosomal S6 kinase (S6K), which is a downstream target of AKT and also a feed-back inhibitor of insulin signaling.?Suggest that imidacloprid could induce insulin resistance by affecting the insulin signaling cascade, particularly up-stream of AKT, in adipocytes, liver, and muscle[1].