Aims: Aboriginal peoples have a high prevalence of smoking and are at major risk for diabetes. The role of insulin resistance vs. compromised β-cell function in the link between smoking and glycaemic disease is not clear. This study tested whether relations between insulin resistance and β-cell function differ between current smokers, former smokers and non-smokers, and if having diabetes modifies smoking-related effects. Methods: A community-based diabetes screening initiative was mounted for a North-western First Nation (Interior Salishan) in rural British Columbia, Canada. Respondents were on-reserve Aboriginal people (n = 156), all adults 18 + years. Glycaemic status was determined by oral glucose tolerance test. Fasting values for glucose and insulin were used to estimate β-cell function and insulin resistance by homeostasis model assessment (HOMA). Analyses adjusted for age, sex, alcohol intake, education, body mass index and physical activity. Results: For normoglycaemic persons (n = 119) current smokers relative to non-smokers had high β-cell values [difference (95% confidence interval) 19.5 (17.1, 21.9)], while former smokers had low β-cell values [difference -22.8 (-20.3, -25.3)] (P < 0.0001). For diabetic persons (n = 37) differences were of equivalent direction but greater magnitude (P < 0.0001). Insulin resistance was for normoglycaemic persons highest for current smokers, and for diabetic persons lowest for current smokers (P = 0.021). Conclusions: Former smoking is associated with low β-cell function, and current smoking with high β-cell function, independent of diabetes in the Northwestern First Nation surveyed. Associations between smoking and insulin resistance vary according to glycaemic status. Smoking may have diametric acute and post-cessation effects on β-cell function and insulin resistance.