BACKGROUND: Impaired insulin sensitivity could be an intermediate step that links exposure to air pollution to the development of type 2 diabetes. However, longitudinal associations of air pollution with insulin sensitivity remain unclear. Our study investigated the associations of long-term air pollution exposure with the degree and rate of change of insulin sensitivity. METHODS: In this longitudinal study, we analysed data from the Cooperative Health Research in the Region of Augsburg (KORA) cohort from Augsburg, Germany, which recruited participants aged 25-74 years in the survey between 1999 and 2001 (KORA S4), with two follow-up examinations in 2006-08 (KORA F4) and 2013-14 (KORA FF4). Serum concentrations of fasting insulin and glucose, and homoeostasis model assessment of insulin resistance (HOMA-IR, a surrogate measure of insulin sensitivity) and ß-cell function (HOMA-B, a surrogate marker for fasting insulin secretion) were assessed at up to three visits between 1999 and 2014. Annual average air pollutant concentrations at the residence were estimated by land-use regression models. We examined the associations of air pollution with repeatedly assessed biomarker levels using mixed-effects models, and we assessed the associations with the annual rate of change in biomarkers using quantile regression models. FINDINGS: Among 9620 observations from 4261 participants in the KORA cohort, we included 6008 (62·5%) observations from 3297 (77·4%) participants in our analyses. Per IQR increment in annual average air pollutant concentrations, HOMA-IR significantly increased by 2·5% (95% CI 0·3 to 4·7) for coarse particulate matter, by 3·1% (0·9 to 5·3) for PM2·5, by 3·6% (1·0 to 6·3) for PM2·5absorbance, and by 3·2% (0·6 to 5·8) for nitrogen dioxide, and borderline significantly increased by 2·2% (-0·1 to 4·5) for ozone, whereas it did not significantly increase for the whole range of ultrafine particles. Similar positive associations in slightly smaller magnitude were observed for HOMA-B and fasting insulin levels. In addition, air pollutant concentrations were positively associated with the annual rate of change in HOMA-IR, HOMA-B, and fasting insulin. Neither the level nor the rate of change of fasting glucose were associated with air pollution exposure. INTERPRETATION: Our study indicates that long-term air pollution exposure could contribute to the development of insulin resistance, which is one of the key factors in the pathogenesis of type 2 diabetes. FUNDING: German Federal Ministry of Education and Research.