Objective To compare the clinical characteristics of diabetes mellitus (DM) patients complicated with pyogenic liver abscess (PLA) and non-DM (NDM) patients complicated with PLA, and provide evidence for clinical diagnosis and treatment. Methods PLA patients who admitted to an affiliated hospital of Anhui Medical University from July 2002 to February 2022 were selected and divided into DM+PLA group and NDM+PLA group according to whether they had DM. General condition, clinical manifestations and signs, complications, biochemical and patho- genic examination results, imaging findings, as well as clinical efficacy and influencing factors of the two groups of patients were analyzed retrospectively. Results 695 PLA patients were included in the analysis, 191 (27.5%) in the DM+PLA group and 504 (72.5%) in the NDM+PLA group. The proportions of males and complication of hypertension in the DM+PLA group were higher than those in the NDM+PLA group, while the proportion of bi-liary diseases and malignant tumors was lower (all P < 0.05). The proportions of patients developing fever, fatigue, as well as concurrent anemia and hypoalbuminemia in the DM+PLA group were higher than those in the NDM+PLA group (all P < 0.05). Compared with the NDM+PLA group, the neutrophil count and percentage in the DM+PLA group increased, while total protein, albumin content, and albumin/globulin ratio all decreased (all P < 0.05). The proportions of the detection of Klebsiella pneumoniae and the occurrence of liver right lobe abscess in DM+PLA patients were higher than those of the NDM+PLA group (both P < 0.05). Multivariate logistic regression analysis revealed that malignant tumor was a risk factor for affecting the clinical efficacy of PLA patients, invasive treatment was a protect factor for affecting the clinical efficacy of PLA patients, while blood sugar was a risk factor for affecting the clinical efficacy of NDM+PLA patients. Conclusion DM+PLA patients have more severe infection symptoms than NDM+PLA patients, and are accompanied by higher proportions of Klebsiella pneumoniae infection and liver right lobe abscess. It is necessary to strengthen attention to patients with malignant tumor and control blood sugar level, and timely supplement with invasive treatment if necessary.