OBJECTIVE To examine the association of seal oil and salmon consumption with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) among Alaska Natives. RESEARCH DESIGN AND METHODS Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians ≥40 years old in 15 villages. Self-administered questionnaires were used to obtain partial food frequency data. A case was defined as IGT or NIDDM, either newly discovered or known. Newly discovered cases (11 patients with NIDDM and 17 with IGT) were determined by random blood glucose testing followed by a 2-h 75-g oral glucose tolerance test (OGTT) for those with values ≥ 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance. Known cases included 26 patients with NIDDM and 1 with IGT. Control subjects had random blood glucoses RESULTS Compared with less-than-daily consumption, both daily seal oil (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1–0.8) and daily salmon consumption (OR 0.5, CI 0.2–1.1) were associated with a lower prevalence of glucose intolerance, controlling for age, ethnicity, body mass index, and sex. The effects were similar when limited to newly discovered cases: OR 0.3, CI 0.1–1.3 for seal oil and OR 0.4, CI 0.1–1.3 for salmon. Consumption of seal oil at least five times per week was required to reduce risk. CONCLUSIONS Consumption of seal oil and salmon, high in ω-3 fatty acids, appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives.