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BACKGROUND Peanut skin procyanidins (PSP) have been shown to possess anti-diabetic activities. However, the mechanism remains poorly understood due to its low bioavailability. This study aims to investigate the preventive effect of PSP on type 2 diabetes (T2D) in mice through regulating gut microbiota and gut barrier in mice with streptozotocin (STZ)-induced type 2 diabetes (T2D). During the 30 consecutive days of the study, T2D mice were administered PSP intragastrically at 75, 150 and 300 mg kg/body weight per day. RESULTS PSP treatment obviously alleviated glucolipid metabolism disorders, decreased the levels of LSP, IL-6, TNF-α, and increased that of IL-10. PSP treatment enhanced the abundance of Lachnospiraceae_NK4A136_group, Alloprevotella, Akkermansia and Faecalibaculum and reduced that of Muribaculaceae. Some of these were associated with the production of short chain fatty acids and anti-inflammatory effect, suggesting their important roles in T2D mice. More importantly, PSP improved the gut barrier integrality by restoring gut morphology and enhancing tight junction protein expression including ZO1, claudin1 and occludin in colon. Subsequently, PSP ameliorated insulin resistance by decreasing LPS/TLR4/JNK inflammatory response, and enhancing IRS1/PI3K/AKT insulin signaling pathways in the liver. CONCLUSION PSE may alleviate the symptoms of T2D by mitigating inflammatory response, modulating gut microbiota and improving intestinal integrity. This article is protected by copyright. All rights reserved.