Abstract Our research aims to evaluate the function of the STAMP 2 gene, an important trigger in insulin resistance ( IR ), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP 2 was measured by RT ‐ PCR and W estern blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL . Correlation of STAMP 2/Akt signaling pathway and macrophage apoptosis was validated by Ad‐ STAMP 2 transfection and STAMP 2 si RNA inhibition. The diabetic mice showed typical features of IR , hyperglycaemia. Overexpression of STAMP 2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP 2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro , both m RNA and protein expressions of STAMP 2 were increased under high glucose treatment. P‐Akt was highly expressed and caspase‐3 was decreased after overexpression of STAMP 2. However, expression of p‐Akt protein was decreased and caspase‐3 was increased when STAMP 2 was inhibited by si RNA . STAMP 2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.