Objective: Crocin, a bioactive component of saffron, has many biological effects such as antioxidant property. The present study investigated the anti-hyperglycemic, anti oxidant and immunomodulatory effects of crocin on streptozotocin-induced diabetic rats. Method: In this study, the rats were divided into the following groups of 9 animals each: control, untreated diabetic, three crocin (10, 20, 30 mg/kg/day)-treated diabetic groups. Diabetes was induced by streptozotocin in rats. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. Crocin (intraperitoneal injection) was administered 3 days after streptozotocin administration; these injections were continued to the end of the study (4 weeks). At the end of the 4 week period, blood was drawn for biochemical assays and abdominal aorta was removed for detecting the inflammatory cytokines expression. Results: Ours results showed that the crocin decreased blood glucose, malondialdehyde, nitric oxide, total lipids, triglycerides, cholesterol levels significantly (p < 0.01) and increased glutathione level, catalase and superoxide dismutases activities in the crocin-treated diabetic groups compared with the untreated groups, in a dose dependent manner (p < 0.05, p < 0.01, p < 0.001). On the other hand, crocin-treated diabetic rats inhibited the expression of inflammatory cytokines in abdominal aorta, with respect to the untreated diabetic rats. Conclusions: These results validate the use of crocin as a treatment against diabetes mellitus and its complications and suggest it is suitable to continue studies for its safe therapeutic use. (C) 2016 Elsevier Ltd. All rights reserved.