Background: Patients with type I diabetes are at increased risk of osteoporosis even after insulin therapy in adult stage. This study was conducted to compare the efficacy of hesperidin (hesp) therapy versus that of insulin alone in the alleviation of osteoporosis arising from type I diabetes mellitus (T1DM) in young rats. Materials and methods: Hesperidin was administered orally to STZ-induced diabetes. The animals were evaluated morphologically and biochemically and compared with that received daily SC injections of long-acting insulin. Results: Histologically, we observed the degeneration of osteoblasts and osteocytes, decreased collagen fibers, and disturbed bone turn over markers in untreated DM rats. Hesperidin+ insulin supplementation to diabetic rats caused significant improvement of most of the bone histological and morphometric parameters compared with the insulin-treated group. Furthermore, hesp treatment significantly reduced pro-inflammatory mediators TNF alpha and NF-kappa B and increased serum biochemical markers of bone turnover, including osteopontin (OPN), osteocalcin (OC) and decreased serum alkaline phosphatase (ALP). Conclusion: These data demonstrated that hesp could be considered to be a beneficial drug for preventing diabetic osteoporosis in growing age. (C) 2017 Elsevier GmbH. All rights reserved.