Aim To explore the key members of the miRNAs target to peroxisome proliferator-activated receptor γ(PPARγ), and reveal the clinical significance of which are closely related to in-stent restenosis(ISR). Methods Cytoscape and its plug-in was used to build the miRNAs-PPAR regulatory network to screen out which are the key miRNAs target to PPARγ. The expression of miRNAs in ISR group were detected by Real-time PCR and the clinical recognition ability of miRNAs on ISR patients were evaluated by ROC curve. Results By bioinformatics analysis, miR-27a/b has a strong regulatory effect on PPARγ, while miR-130a/b is able to regulate more genes in the network. Real-time PCR found that miR-27a/b and miR-130a were differentially expressed in the ISR group and no-ISR group (P<0.05). ROC curve analysis showed that miR-27a has a certain clinical recognition ability to ISR (AUC =0.4,5% CI 0.768~1.00, P<0.001). Conclusion MiR-27a/b and miR-130a/b are key members of the miRNAs target to PPARγ, miR-27a/b and miR-130a were differentially expressed in ISR, miR-27a might have certain clinical diagnostic value in patients with ISR.