Abstract: Objective To investigate the relationship between serum galectin-3 and in-stent coronary stenosis (ISR) in patients with type 2 diabetes mellitus and coronary heart disease. Methods Patients with type 2 diabetes mellitus complicated with coronary heart disease and previous drug-eluting stent (DES) implantation treated in Zhejiang Hospital from January 2015 to January 2016 were included. According to the results of coronary angiography, all patients were classified into ISR group and non-ISR group. The relationship between clinical data and ISR was analyzed by multivariate logistic regression. Results A total of 357 patients were enrolled, of whom 36 were in group ISR (10.1%). Compared with non-ISR group, ISR group had higher age, proportion of smokers, serum Galectin-3 level, longer stent length and smaller stent diameter (P<0.05). Multivariate logistic regression analysis showed that age (OR=1.087, 95% CI: 1.038-1.134, P<0.001), stent length (OR=1.078, 95% CI: 1.012-1.103, P<0.001), stent diameter (OR=0.425, 95% CI: 0.243-0.708, P<0.001) and serum Galectin-3 level (OR=1.074, 95% CI: 1.016-1.121, P<0.001) were independent risk factors for ISR. In addition, serum Galectin-3 level was correlated with ISR type. Conclusion High serum Galectin-3 level increases the risk of ISR in type 2 diabetes mellitus, which may be an independent risk factor for ISR. This provides a new idea for the application of serological markers in assessing the severity of coronary artery disease.