An adult female Border Collie was referred for treatment of a difficult to control diabetic ketoacidosis (DKA). The patient’s clinical signs and findings were consistent with DKA, however institution of standard treatment protocols and hospitalization over 7 days failed to mitigate the patient’s ketonemia or anorexia. Testing revealed two possible explanations for the patient’s insulin resistance: an intact reproductive tract found on abdominal ultrasound and a mass on the right 5th mammary gland. Ovariohysterectomy and excisional mammary mass biopsy were performed. All tissues were submitted for histopathology. Within one week of surgery, the patient’s ketonuria and anorexia had resolved with standard insulin therapy. Histopathology revealed multiple corpora lutea, ovarian cysts, and endometrial hyperplasia. The mammary mass was found to be fibroadenomatous change. These findings suggest that this was a case of diestrus-related diabetes mellitus. This case report will discuss the pathogenesis and treatment of DKA in addition to the unique mechanisms of progesterone-mediated insulin resistance in dogs.