Objective To investigate the correlation between chapossidase-3-like protein 1 (CHI3L1) and intimal hyperplasia in venous outflow of arteriovenous fistula (AVF) in hemodialysis patients with diabetes.  Methods A total of 30 patients diagnosed with end-stage renal disease and receiving maintenance hemodialysis via AVF at the Department of Nephrology, Zhoushan Hospital from January 2023 to December 2023 were enrolled in this study. They were divided into diabetes group (n=15) and non-diabetes group (n=15). General data, AVF reconstruction surgery, dialysis, and laboratory results were collected. Glucose and lipid metabolism indicators were measured, and the correlation between these indicators and the intimal hyperplasia was analyzed. A segment of 0.5cm cephalic vein sample from venous outflow of the AVF was obtained during AVF reconstruction surgery. The samples were subjected to hematoxylin-eosin staining, van Gieson staining for elastic fibers, and immunohistochemistry and western blot for CHI3L1 expression.  Results Patients in diabetes group exhibited increased thickness of intima and media and higher ratio of intima-media thickness of the cephalic vein samples compared with those in non-diabetes group (t=14.642, 12.547, and 27.462, respectively; P＜0.001). Moreover, CHI3L1 expression increased significantly in diabetes group than in non-diabetes group (t=7.888, P＜0.001). Fasting blood glucose (OR=0.243, 95% CI: 0.086～0.687, P=0.008), glycated hemoglobin (OR=0.039, 95% CI: 0.002～0.701, P=0.028), triglycerides (OR=0.235, 95% CI: 0.042～0.875, P=0.048), total cholesterol (OR=0.096, 95% CI: 0.015～0.629, P=0.015), and low-density lipoprotein cholesterol (OR=0.214, 95% CI: 0.079～0.580, P=0.002) were the independent risk factors for intimal hyperplasia in venous outflow of AVF in hemodialysis patients with diabetes mellitus. CHI3L1 expression was positively correlated with the intimal hyperplasia (r=0.717, P＜0.001).  Conclusion Intimal hyperplasia in the venous outflow of AVF is closely correlated with the higher CHI3L1 expression, which may serve as a potential biomarker for intimal hyperplasia in AVF in hemodialysis patients with diabetes. Abnormal glucose and lipid metabolism may aggravate intimal hyperplasia in AVF through intimal injury and inflammation activated CHI3L1 expression.