These in vivo and in vitro studies demonstrate that 1) CREBZF deficiency in macrophages improves insulin sensitivity via the crosstalk between ATM and adipocytes; 2) CREBZF promotes NF‐κB signaling by competitively inhibiting the binding of IκBα to p65; 3) Pharmacological inhibition of CREBZF corrects ATM activation and type 2 diabetes in mice; 4) CREBZF is highly expressed in ATM of obese humans and mice, which is correlated with proinflammation genes and insulin resistance in humans. This evidence concerns the gene CREBZF and Insulin resistance.