Objective: We evaluated the association between baseline urinary N-acetyl-β -D-glucosaminidase (NAG) and the progression of carotid artery atherosclerosis. Methods: This study was retrospective longitudinal study which enrolled patients with type 2 diabetes mellitus (T2D) who had undergone carotid IMT measurement twice and baseline laboratory measurement including urinary NAG. The subjects were classified to two groups based on the change of IMT; non-progression group and progression group. Baseline urinary NAG was compared between two groups. Correlation and regression analysis were also conducted to verify whether urinary NAG predicts the progression of carotid IMT. Results: Of the 75 patients, progression group (n = 50) showed significantly higher baseline urinary NAG, and follow-up results of carotid IMT than non-progression group (n = 25). When we conducted Spearmen’s correlation test, urinary NAG was significantly associated with progression of carotid IMT (Δ IMT). In multivariate logistic regression analysis, urinary NAG predicted the progression of IMT after adjustment for other conventional risk factors. Conclusion: Baseline urinary NAG is significantly associated with the progression of carotid IMT. It also might be a predictive factor for the progression of carotid arterial atherosclerosis.