n-3 Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and taurine are functional compounds abundantly present in seafoods. In this study, we examined the combined effects of EPA- and DHA-rich fish oil and taurine on white adipose tissue (WAT) weight and blood glucose levels in diabetic/obese KK-A(y) mice. After a 4-wk administration of experimental diets (soybean oil or fish oil, supplemented with 0%, 2%, or 4% taurine), the increase in WAT weight of the mice fed the "fish oil + 4% taurine" diet was significantly suppressed compared to the "soybean oil + 4% taurine" and "fish oil only" diets. Serum triglycerides, free fatty acids, and total cholesterol levels decreased by fish oil administration. In addition, fish oil and taurine increased the activity of acyl-CoA oxidase, which is the rate-limiting enzyme of peroxisomal β-oxidation, increased in the liver of KK-A(y) mice. The activity of fatty acid synthase decreased by fish oil diets. Furthermore, blood glucose and insulin levels were significantly lower in the mice fed fish oil than in the soybean oil-fed mice. In fish oil + 4% taurine group, hyperglycemia and hyperinsulinemia were effectively improved in KK-A(y) mice compared to the fish oil only groups. In particular, the combination of fish oil and taurine enhanced the glucose transporter 4 (GLUT4) distribution in the plasma membrane of muscle tissue. These results suggest that EPA- and DHA-rich fish oil, especially in combination with taurine, exhibits preventive effects on WAT weight gain and hyperglycemia in diabetic/obese KK-A(y) mice.