Objective To investigate the relationship between soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and atherosclerotic plaque formation in patients with type 2 diabetes mellitus (T2DM).Methods A total of 73 T2DM patients hospitalized in Department of Endocrinology of The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Jun. to Dec. 2017 were enrolled, and were divided into plaque group (46 cases) and non-plaque group (27 cases). General data, blood biochemical indexes and serum sTWEAK levels of the 2 groups were compared. The correlation between sTWEAK and each clinical index was evaluated using Spearman correlation analysis. Influencing factors of atherosclerotic plaque formation were evaluated using logistic regression analysis.Results Compared with non-plaque group, the age and serum sTWEAK level were significantly higher in the plaque group ([55.87±10.65] years old vs [44.04±11.96] years old, P＝0.001; 79.53 [26.87, 113.03] pg/mL vs 47.70 [18.62, 78.15] pg/mL, P＝0.018). Spearman correlation analysis showed that serum sTWEAK level was positively correlated with age (r＝0.247, P＝0.035) and number of plaques (r＝0.270, P＝0.021). Logistic regression analysis showed that age was an independent risk factor of atherosclerotic plaque formation in T2DM patients (odds ratio [OR]＝1.091, 95% confidence interval [CI] 1.036-1.148, P＝0.001), while serum sTWEAK was not an independent risk factor (OR＝1.012, 95% CI 0.999-1.025, P＝0.063).Conclusion T2DM patients with atherosclerotic plaques have higher serum sTWEAK levels, and the increase of serum sTWEAK levels may be related to age.