Objective To explore the effect of chronic high glucose on mouse macrophages in vitro and its mechanism. Methods RAW264.7 macrophages were cultured in normal growth medium and glucose-containing 40 or 60 mmol/L growth medium for 1, 3, 5 and 7 days. Cell morphology was observed by phase contrast microscopy; cell proliferation was measured by CCK-8 assay; interleukin-1β (IL-1β) and IL-10 protein levels were detected by Western blot analysis; IL-1β and IL-10 secretion were detected by ELISA; the levels of AKT mRNA in the cells were tested by real-time quantitative PCR; the levels of AKT and phosphorylated AKT (p-AKT) were examined by Western blot analysis. Results After 60 mmol/L glucose treatment for 1 day, the longer spindle cells appeared, the extended pseudopod was visible, and the number and volume increased over time. After treatment for 1 day, cell proliferation was significantly inhibited, and the inhibitory effect was ameliorated with time. After treatment for 3, 5, and 7 days, IL-1β protein level increased and IL-10 protein level decreased. After treatment for 1 day, the secretion of IL-1β increased significantly, but after treatment for 3 days, the secretion of IL-10 decreased significantly and decreased further over time. AKT protein phosphorylation was inhibited after treatment for 3, 5, and 7 days, but AKT mRNA level did not change obviously. Glucose (40 mmol/L) treatment played a role to some extent, but it was not as significant and stable as 60 mmol/L glucose. Conclusion Chronic high glucose induces macrophages to transform into pro-inflammatory M1 type and the continuous chronic inflammatory response, which may be related to the inhibition of AKT protein phosphorylation.