Aim To investigate whether atherosclerotic plaque inflammation is increased and the related mechanisms in atherosclerotic plaques in diabetic apolipoprotein E-deficient mice. Methods Male apolipoproteinE-deficient mice were injected with 60 mg/(kg·d)streptozotocin for 5 days to induce diabetes and mice with fasting glucose>10 mmol/L were included to diabetic mellitus group (n=8), control mice (n=8) were injected with citrate buffer. The levels of serum total cholesterol, glucose and advanced glycation end-products in apolipoproteinE-deficient mice were dectected in 8 and 22 weeks. The expression of receptor for advanced glycation end-products, cyclooxygenase-2, microsomal prostaglandin E synthase-1 and metalloproteinase-9 were determined by immunohistochemistry and Western blot. Immunohistochemistry was also used to identify CD68+ macrophages, CD3+ T-lymphocytes, α-smooth muscle actin, CD31+ endothelia cells and collagen. Results Compared with control group, diabetic mellitus group had higher serum total cholesterol, glucose (P<0.01), and advanced glycation end-products(P<0.05) levels. Atherosclerotic plaques in diabetic apolipoproteinE-deficient had larger area and more macrophages, cyclooxygenase-2, microsomal prostaglandin E synthase-1(P<0.05), Lipid, T-lymphocytes, receptor for advanced glycation end-products, and metalloproteinase-9 (P<0.01), reduced α-smooth muscle actin and collagen content (P<0.01). Conclusions These data suggest that diabetes mellitus is associated with enhanced inflammatory reaction, and these changes may contribute to increased instabability in diabetic plaques.