Context: Epidemiological studies indicate that diabetes is a sub-population at risk for particulate matter (PM)-associated cardiovascular disease (CVD). Recent animal studies suggested PM might impair glucose tolerance, which may lead to CVD. However, the mechanism remains unclear. Objective: To investigate further the PM effect on insulin resistance (IR) in obese and healthy rats. Materials and methods: Male Sprague-Dawley rats were fed with either a high fat diet (HFD) or normal chow diet (NCD) for 6 weeks. Both groups were then further assigned to receive PM(10), PM(2.5) or normal saline (n = 6 per group) by intratracheal instillation (IT) once per week for 3 weeks. Fasting glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess IR. Biochemistry tests and lipids profile were examined at sacrifice. The markers of fibrinogen and [nitrate + nitrite], an indicator of nitric oxide (NO) production, C-reactive protein (CRP) and white blood counts (WBCs) in peripheral blood were also determined. Results: Body weight, insulin and HOMA-IR of HFD rats were significantly increased compared with a NCD after 6 weeks. In HFD rats, PM(2.5) increased HOMA-IR after first IT and further increased HOMA-IR at the end of exposure. However, this increase was not observed in NCD rats and after PM(10) exposure. Increased fibrinogen was also noted after chronic PM(2.5) exposure in both HFD and NCD rats. Discussion and conclusion: Exposure to PM(2.5) enhanced IR in HFD rats but not in NCD rats. Obese subjects with IR may be a susceptible population to particulate air pollution.