In this study, we measured the insulin-like growth factor (IGF)-I levels and evaluated the serum protein profiles of diabetic, insulin-treated, and healthy cats and dogs. The total IGF-I concentrations were 33.74 +/- 3.4 ng/mL for normal, 25.8 +/- 4.5 ng/mL for diabetic, and 180.4 +/- 31.4 ng/mL for insulin-treated cats. IGF-1 concentrations were 46.4 +/- 6.6 ng/mL for normal, 25.1 +/- 4.1 ng/mL for diabetic, and 303.0 +/- 61.3 ng/mL for insulin-treated dogs. Total serum protein profiles were analyzed by SDS-PAGE. Fourteen bands ranging from 25 to 240 kDa in size were observed for cats, and 17 bands ranging from 25 to 289 kDa were observed for dogs. The densities of the bands differed among control, diabetic, and insulin-treated animals. In conclusion, we found that serum protein profiles and IGF-I concentrations were altered in both diabetic and insulin-treated animals. When judiciously interpreted in the light of other clinical and laboratory data, the techniques used in our study provide a valuable modality for measuring the severity of diabetes mellitus in dogs and cats.