Sitagliptin effects on inflammation and fibrosis of endocrine pancreas of diabetic ZDF rats. Endocrine inflammation in 26 week-old animals (images A-C): (A) Micrograph of normal islet of Langerhans observed in a lean control ZDF rat; (B) Islet of Langerhans of an untreated diabetic ZDF rat showing severe inflammatory infiltrate occupying over 50% of the islet’s area (Grade 3 inflammation); (C) A clearly regression of inflammation is observed after 6 weeks of sitagliptin treatment in obese diabetic ZDF rat (Grade 1 inflammation). Endocrine fibrosis observed in 26 week-old animals (images D-F): (D) Normal islet of Langerhans of lean control ZDF rat; (E) Grade 3 fibrosis in an untreated obese diabetic ZDF rat, displaying a large and irregularly shaped islet filled with fibrous tissue, evidenced by intense pink staining; (F) Grade 1 fibrosis in a regular, small islet in sitagliptin treated diabetic ZDF rats. Semiquantitative evaluation of inflammation (graph G) and fibrosis (graph H): (G) A significantly higher (p < 0.001) endocrine inflammation in diabetic rats was recorded when compared to lean control animals. Sitagliptin treatment of diabetic ZDF rats during 6 weeks significantly reduced (p < 0.001) inflammation in comparison to untreated counterparts; (H) Data for endocrine fibrosis showed a trend for an increase in diabetic rats when compared to lean control animals, and a trend for improvement with sitagliptin treatment, although without statistical significance. Chi-square test with Monte Carlo simulation or exact test (when contingency tables are 2 × 2) was performed to find out the differences in histomorphological lesions observed in endocrine pancreas. (p < 0.05, p < 0.01 and p < 0.001 for one, two or three symbols, respectively; n = 5 per group).