The study aimed to investigate the value of plasma alpha 2-Heremans-Schmid glycoprotein (AHSG) levels for predicting the presence and severity of lower extremity atherosclerosis disease (LEASD) in Yi Chinese patients with type 2 diabetes mellitus (T2DM). A total of 128 consecutive patients with T2DM and 120 normal controls were recruited. Plasma AHSG levels were analyzed by enzyme-linked immunosorbent assay (ELISA). LEASD was diagnosed by color Doppler ultrasound examination, and its severity was assessed by the sum of each atheroscle-rosis (AS) score, including intima-media thickness (IMT), degree of sclerosis, plaques, and luminal stenosis. T2DM subjects had significantly higher AHSG levels than normal controls (348.88±48.18 μg/ml vs. 283.09±40.72 μg/ml, P < 0.01). T2DM patients with LEASD showed significantly higher AHSG levels than T2DM patients without LEASD (363.80±48.35 μg/ml vs. 332.48±42.66 μg/ml, P < 0.01). The difference remained statistically significant after adjusting for all other potential confounders between groups using covariance analysis. AHSG was positively correlated with homeostasis model assessment-insulin resistance (HOMA-IR) and AS scores by Pearson’s correlation analysis (r = 0.175, P < 0.05; r = 0.407, P < 0.01, respectively). HOMA-IR was independently associated with AHSG in a multivariate linear regression analysis (t = 2.150, P < 0.05). Logistic regression analysis revealed that AHSG was an independent risk factor for T2DM and for T2DM complicated by LEASD (OR = 1.070, 95% CI: 1.027-1.116, P < 0.01; OR = 1.024, 95% CI: 1.011-1.037, P < 0.01, respectively). An increased level of plasma AHSG might serve as a potential predictor of the presence and development of T2DM and LEASD caused by T2DM in Yi Chinese patients. © 2016, E-Century Publishing Corporation. All rights reserved.