Objective: To investigate the therapeutic effect of TDZD-8 (4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione) on acute pancreatitis in mice. Methods: Fifty-four BALB/c mice were equally randomized into control group, model group and treatment group. The mice in model group and treatment group were subjected to intraperitoneal injection of caerulein (50 μg/kg per hour, 13 times) to induce AP, while the mice in control group were treated with normal saline of the same volume in the same fashion, and mice in treatment group were intraperitoneally injected with 10 mg/kg TDZD-8 at 30 min after the last caerulein injection. At 3, 6 and 12 h after the last caerulein injection, 6 mice at each time point in each group were sacrificed. Then, the blood levels of amylase and interleukin 6 (IL-6) were measured, the pancreatic pathology was assessed by HE staining and nuclear factor κB (NF-κB) expression in the pancreatic tissue was determined by immunohistochemical staining. Results: Compared with control group, in model group and treatment group, the blood levels of amylase and IL-6, and pathological scores and NF-κB expressions in pancreatic tissues were all markedly increased, and were gradually increased with time prolongation, while all values of above parameters in treatment group were lower than those in model group; all the differences reached statistical significance (all P<0.05). Conclusion: TDZD-8 has protective effect against acute pancreatitis in mice, and the mechanism is probably associated with its inhibition of NF-κB activity and thereby attenuate the inflammatory response.