Objective To estimate the optimal dose of gemcitabine administered concurrently with gamma knife therapy in patients with locally advanced pancreatic cancer. Method “3+3” model was measured in the study. Eligible patients had histologically confirmed pancreatic adenocarcinoma deemed locally unresectable. Patients received gamma knife therapy (52 Gy/13F) with concurrent infused weekly gemcitabine(dose escalated from 700 mg/m² to 900 mg/m² weekly) until dose-restricted toxicity. Results 9 patients were enrolled. Patients enrolled in gemcitabine 700 mg/m² and 800 mg/m² completed the plan.III-IV degree hematology toxicity was seen in patients when gemcitabine dose escalated to 900 mg/m². Conclutions The combination of gemcitabine and gamma knife therapy is well tolerated. The optimal dose of gemcitabine is 800 mg/m² weekly.