Abstract: The purpose of this study was to assess the effects of vasoactive intestinal peptide (VIP) administration on the glycemic state, insulin secretion, various pro-inflammatory and anti-inflammatory cytokines, liver pathology and oxidative stress as well as antioxidant defense system in streptozotocin-induced diabetic mice. VIP was intraperitoneally administered to normal and streptozotocin-induced diabetic CD1 mice at a dose level of 41.6 ng kg-1 b.wt., 3 times/week for 8 consecutive weeks to form a total dose of 1 μg kg-1 b.wt. at the end of the experiment. The VIP was found to have anti-hyperglycemic and insulinotropic properties and improving effects on the islets of Langerhans and liver pathology of diabetic mice. These VIP ameliorating-changes may be mediated via its augmenting effect on anti-inflammatory cytokines (IL-10 and IL-12) and decreasing effect on pro-inflammatory cytokine, TNF-α, as well as its potency in suppressing the oxidative stress and enhancing the anti-oxidant defense system. However, further clinical studies are required to assess the efficacy and safety of VIP in diabetic human beings.