Aim To explore the predictive value of red blood cell distribution width (RDW) for in-stent restenosis (ISR) after coronary stenting with drug-eluting stent (DES) in patients of type 2 diabetes. Methods The study retrospectively searched data at Tianjin Nankai Hospital for 582 unstable angina pectoris patients with type 2 diabetes who underwent PCI from January 2012 to December 2016. Among these patients, 292 patients with coronary DES implantation were enrolled in this study. The ISR was analyzed by coronary angiography analysis at a mean follow-up of eight months. According to whether ISR was detected, type 2 diabetes patients were divided into two groups:the ISR group (n=45) and the non-ISR group (n=247). Patients' clinical and demographic characteristics were recorded including age, gender, smoking, anamnesis, RDW, C-reactive protein (CRP), cardiac ultrasound, coronary angiography, and so on. Results The body mass index (BMI) levels were higher in the ISR group than that in the non-ISR group (P<0.05). Patients with ISR had higher smoking rates (P<0.05). In addition, patients in the ISR group had significantly higher RDW levels compared with patients in the non-ISR group both at admission and at follow-up (P<0.01, respectively). Furthermore, the ISR group had significantly longer stent length and lower stent diameter compared with the non-ISR group (P<0.01, respectively). In an univariate model using RDW as a continuous variable, there was a significantly positive association between RDW levels and the incidence of ISR (P<0.01). Further multivariate logistic regression analysis revealed that BMI, smoking, RDW, CRP, stent length, and stent diameter were associated independently with ISR. Conclusion Elevated RDW has predictive value for ISR occurrence in type 2 diabetes patients with coronary DES implantation, which indicates that a chronic inflammatory response might be involved in the pathogenesis of ISR.