Abstract: Objective：To investigate the role and relationship of serum ferritin (SF) and β2 microglobulin (β2M) in the pathogenesis of diabetic patients complicated with lacunar infarction (LI). Methods：A total of 127 patients with LI confirmed by magnetic resonance were divided into diabetes mellitus combined with LI group and non-diabetic LI group according to whether they had diabetes or not. In addition, physical examinees matched with age and sex were taken as control group. The number of SF, β2M, LI, and other related indicators of each group were detected and compared. Pearson linear correlation analysis and multiple stepwise linear regression analysis were used to analyze the correlation between SF, β2M, and LI, as well as the correlation between the three and HbA1c levels and their influencing factors. Results：The levels of SF and β2M in the diabetic group were significantly higher than those in the non-diabetic group (P<0.01). The number of LI in the diabetes mellitus combined with LI group was higher than that in the non-diabetic LI group (P<0.01). The number of SF, β2M, and LI was positively correlated with HbA1c level (P<0.01); SF was positively correlated with LI number (P<0.01); there was no correlation between β2M and LI number. Regression analysis suggested that HbA1c was an independent influencing factor of SF levels in patients with diabetes mellitus and LI; HbA1c and systolic blood pressure were independent influencing factors of β2M; SF was an independent influencing factor of LI number. Conclusions：The numbers of SF, β2M, and LI in patients with diabetes mellitus complicated with LI is higher than that in non-diabetic patients with LI. SF plays an important role in the development of diabetes mellitus combined with LI, which may be a predictor of diabetes mellitus combined with LI.