Objective: To evaluate the antioxidant and antidiabetic mechanism(s) of ethyl acetate extract fraction of Moringa oleifera (M. oleifera) leaves on streptozotocin-induced diabetes in male Sprague-Dawley rats. Methods: A total of 24 adult male rats were segregated randomly into four groups (6 rats each group). Streptozotocin-induced diabetes rats were given (oral gavage) ethyl acetate extract fraction of M. oleifera (200 mg/kg b.w.) for 30 d. The rats of control and experimental groups were sacrificed after 24 hours of final dose of treatment, to extract blood and pancreatic tissue for biochemical and histopathological analysis. Results: The ethyl acetate extract fraction of M. oleifera significantly reversed (P<0.05) the manifestation of streptozotocin on the levels of serum glucose & insulin, lipid profile, hepatic damage markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase), malondialdehyde formation, antioxidants (glutathione, Vitamin C & Vitamin E), antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) and pro-inflammatory cytokines (IL-1 β , TNF- α & IL-6). Histopathological analysis of pancreatic tissues was in concurrence with the biochemical results. Conclusions: These findings support that M. oleifera leaves have potent therapeutic effect on diabetes mellitus via increasing antioxidant levels and inhibition of pro-inflammatory mediators.