Abstract： Objective To explore the expression and significance of hedgehog signal molecules (Ptch, Smo and Gli1 ) in pancreatic cancer. Methods Two hundred SD rats were randomly divided into DMBA group ( group A, n = 90), cyclopamine intervening group ( group B, n = 90) and control group ( group C, n = 20).For group A and B, DMBA was directly implanted into the parenchyma of the pancreas to establish the model of pancreatic cancer. The rats in group B were treated with 6.25 ml/kg cyclopamine and DMSO solution intraperitoneally daily. All rats were sacrificed four months later to observe the pancreatic tissue pathologic changes, and immunohistochemistry SP was used to detect the expression of Ptch, Smo, Gli1 protein in pancreatic cancer and normal pancreatic tissue. Results The prevalence rate of pancreatic cancer in group A was 57.5％ (46/80), the maximum size of the tumor was 0.5 ～ ＞2 cm; the prevalence rate of pancreatic cancer in group B was 17.1％ ( 14/82), the maximum size of the tumor was 0.5 ～ 2.0 cm, and the difference between the two group was statistically significant (P ＜0.05). The positive expression rate of Ptch, Smo and Gli1 protein was 82.6％, 73.9％ and 65.2％ in DMBA group, and was 50.0％, 42.9％ and 28.6％ in cyclopamine group, and the difference between the two group was statistically significant ( P ＜ 0.05 ). Ptch,Smo and Gli1 protein was expressed in normal pancreatic tissue. Conclusions Direct implantation of DMBA in the parenchyma of rat pancreas can induce pancreatic cancer with a high incidence in a short time.Hedgehog signal protein expression is significantly increased, cyclopamine can inhibit the occurrence and progression of pancreatic cancer by inhibiting Hedgehog messenger expression.