Purpose: To investigate the effect of colchicine on acute pancreatitis (AP) in a rat model, and the molecular mechanism involved. Methods: Acute pancreatitis (AP) was induced in rats by injection with 5 % sodium taurocholate. Changes in histology of pancreatic tissues were determined following treatment with colchicine. Serum amylase activity was measured using Automated Biochemistry Analyser. Results: Hematoxylin and eosin (H & E) staining showed that colchicine prevented histopathological changes such as infiltration of interstitial leukocytes and erythrocytes, cell necrosis, oedema formation and vacuolization in the rat pancreas. Treatment of AP rats with colchicine significantly and dose-dependently decreased ascite volume in the abdominal cavity. Serum amylase activity was significantly suppressed in AP rats on treatment with 100 mg/kg colchicine. Furthermore, treatment of the AP rats with colchicine caused marked decrease in the expressions of interleukin 6 and tumor necrosis factor a, and upregulated expressions of IL 10 in serum. Colchicine treatment of AP rats also caused significant increase in CGRP level in the plasma. Conclusion: Colchicine prevents pancreatic tissue damage induced by AP by down-regulating pro-inflammatory cytokines, upregulation of anti-inflammatory cytokines, and enhancing CGRP release. Therefore, colchicine may be useful for the treatment of acute pancreatitis.