Aim To investigate the relationship between changes of beta 2-microglobulin (β2-MG) and in-stent restenosis in patients with coronary heart disease after PCI. Methods 162 patients with coronary heart disease treated by PCI were selected. Serum β2-MG levels were measured 12 hours before operation and 1 year after operation respectively. Coronary angiography was performed 1 year after PCI. The patients were divided into ISR group and control group according to the results of coronary angiography. Spearman correlation analysis was used to evaluate the correlation between β2-MG and Gensini integral and the number of coronary lesion branches. Gensini integral and the number of coronary lesion branches were used to evaluate the degree of coronary stenosis and to analyze the relationship between β2-MG and ISR. Results There was no significant difference in the number of coronary lesions, lesion location and lesion degree. Additionally, there was no significant difference in blood chemical change between the two groups 12 hours before operation and 1 month after operation(P>0.05). There was no significant difference in serum β2-MG between the ISI group and the control group before PCI (P>0.05). One month after PCI, the serum β2-MG of the two groups decreased, while it was higher in the ISI group than that of control group (P<0.05). There was no significant difference in the number, location and degree of coronary artery lesions between the two groups before PCI (P<0.05). Multivariate Logistic regression analysis showed that the incidence of ISR after PCI was correlated with the history of diabetes mellitus, difference of β2-MG between 12 hours before PCI and 1 month after PCI (P<0.05). Spearman correlation analysis showed that β2-MG was positively correlated with Gensini score (r=1.231, P=0.025), and the difference of β2-MG between 12 hours before PCI and 1 month after PCI was positively correlated with the number of coronary lesion branches (r=1626, P=0.014). The difference of β2-MG between 12 hours before PCI and 1 month after PCI was analyzed by ROC with ISR as the result variable. The cut-off value was 2.530 mg/L, the area under the ROC curve was 0.758, the standard error was 0.050, the Z value was 2.391, the sensitivity was 84.10%, and the specificity was 72.90%. Conclusions The serum β2-MG level in ISR group was significantly higher than that in non-stenosis group after PCI. The serum β2-MG level was positively correlated with restenosis after PCI, suggesting that β2-MG may be one of the risk factors for ISR after PCI.