A 28-year-old woman with clinical features of acromegaly and diabetes mellitus was admitted to our Reference Center for Clinical Neuroendocrinology and Pituitary Diseases at Sisters of Mercy University Hospital, Zagreb, Croatia. Magnetic resonance scan of the brain showed pituitary macroadenoma. After transsphenoidal resection, histological analysis confirmed it was a growth hormone (GH)-secreting pituitary adenoma. The tumor could not be completely removed, but the hormonal status normalized. A month after the surgery, octreotide was introduced because of a further increase in GH and insulin-like growth factor-I (IGF-I), but discontinued after a week due to intolerance. Alternative treatment with oral antidiabetic agent, rosiglitazone, was introduced two weeks after octreotide was discontinued, and the fasting blood glucose concentration decreased from 8.4 mmol/L before the treatment to 6.7 mmol/L after 90 days of treatment. The concentration of GH and IGF-I in the week before rosiglitazone was introduced was 5.96 ng/mL and 990 ng/mL, respectively, and decreased to 2.92 ng/mL and 180.0 ng/mL, respectively, after 90 days of treatment. There was also a pronounced improvement in acromegalic features. It is possible that rosiglitazone induced the decrease in GH and IGF-I concentrations and its role in the long-term medical therapy of patients with pituitary tumors should be further investigated.