Objective: Activation of pancreatic stellate cells (PSCs) is detrimental to pancreas function by promoting pancreatic fibrosis. Resveratrol is a natural and pharmacologically active compound. This study is to investigate the effect of resveratrol on the bilogical behavior of PSCs under high glucose condition.Methods: Isolated primary mouse PSCs were cultured in low glucose ( 5.5 mmol/L glucose, LG group ) medium, high glucose ( 25 mmol/L glucose, HG group ) medium and treated with resveratrol ( 25 μmol/L or 50 μmol/L). Cell proliferation was examined using MTT assay. The expression of α-SMA and collagen I were determined using Western blotting. Alpha-SMA expression was also determined using immunocytochemistry staining. IL-1, IL-6, and TNF-α mRNA levels and secretion levels in media of PSCs were determined using qRT-PCR and ELISA respectively.Results: Cell Proliferation, α-SMA and collagen I expression levels, IL-1, IL-6, and TNF-α mRNA levels and secretion levels of PSCs were increased after high glucose treatment, compared with low glucose treatment. They were significantly decreased in PSCs treated with both high glucose and resveratrol, compared with high glucose treatment.Conclusion: Resveratrol inhibited high glucose induced PSCs proliferation, activation，cytokine expression and secretion in PSCs. Therefore, resveratrol can be potentially used in therapy of diseases such as type 2 diabetes mellitus (T2DM), pancreatitis and pancreatic cancer where PSCs is activated by high glucose.