Abstract Background Recent studies suggest that people with diabetes or who are at risk of developing diabetes, i.e. prediabetic (preDM), are potentially susceptible to air pollution, but the underlying mechanisms remain unclear because the existing epidemiological studies did not include healthy control groups and only focused on limited health outcomes. We hypothesized that acute exposure to ambient fine particles (PM2.5) will lead to enhanced pulmonary and cardiometabolic changes in preDM than healthy individuals. Methods We recruited 60 preDM and 60 healthy individuals from a community of 22,343 adults in Beijing China, and arranged each subject to complete up to seven repeated clinical visits with measures of 6 cardiopulmonary biomarkers, 6 cytokines, 4 blood pressure and endothelial... function outcomes and 4 glucose metabolism biomarkers.. Moving averaged daily ambient PM2.5 in preceding 1–14 days was matched to each subject and the PM2.5 associated effect on multiple biomarkers was estimated and compared between PreDM and healthy subjects based on linear mixed effect model. Results All the subjects exhibited significant acute elevation of exhaled nitric oxide, white blood cells, neutrophils, interleukin-1α, and glycated haemoglobin with increased exposure to PM2.5. PreDM subjects had significant stronger adverse changes compared to healthy subjects in 6 cardiometabolic biomarkers, namely, interleukin-2, interleukin-8, systolic and diastolic blood pressure, augmentation pressure, and glucose. The maximum elevation of these 6 biomarkers in PreDM subjects were 8.6% [CI: 4.1–13.3%], 10.0% [CI: 3.9–16.4%], 1.9% [CI: 0.2–3.6%], 1.2% [CI: − 0.1-2.4%], 5.7% [CI: − 0.1-11.8%], 2.4% [CI: 0.7–4.2%], respectively, per an interquartile increase of ambient PM2.5 (61.4 μg m− 3) throughout the exposure window of the preceding 1–14 days. No significant difference was observed for the changes in pulmonary biomarkers between the two groups. Conclusions PreDM individuals are more susceptible to the acute cardiometabolic effect of air pollution than the healthy individuals. A considerable public health burden can be inferred, given the high prevalence of prediabetes and the ubiquity of air pollution in China and worldwide.