Objective To develop a percutaneous technique with expandable balloon catheter for establishing a sheep model of acute cervical spinal cord compression injury. Methods Twelve adult male sheep were randomized into 3 groups: control (A, n=4), 0.6 mL compression (B, n=4) and 1 mL compression (C, n=4) groups. All animals received epidural balloon catheter (3Fr) insertion using a percutaneous trans-lumbosacral interlaminar space technique similar to the method used in vascular access for angiography. The balloon catheter was advanced under fluoroscopic guidance until its distal tip reached the C_6/7 level. One week later, the balloons of group B and C were inflated by 0.6 mL and 1 mL half-strength contrast material; the balloons were left inflated for 1-hour and then deflated. Animals in group A received no treatment. CT and MR images were taken before and after surgical procedures. Quantitative assessment of spine canal occupying rate was accomplished by using a software program based on CT results. Motor functions of animals were assessed by modified Tarlov scale. Two animals were sacrificed each time at 24 h and 48 h after inflation in each group. Spinal segments of the injured level were then obtained for pathologic examination. Results Balloon catheters were successfully inserted in all animals, and the spinal-canal-occupying rates were (9.1 ±0.2)% in group A, (9.1±0.2)% in group B, and (8.9±0.2)% in group C after insertion. After inflation, the rates increased to (45.5±2.5)% in group B and (78.3±2.3)% in group C, and MRI findings indicated ventral compression of the cervical spinal cord. Hind limb movement remained normal after catheter insertion in all groups. Animals in group B and C became paraplegic after inflation, and a positive correlation between injection volume and Tarlov score was observed. Pathological results demonstrated neuron atrophy, increased gap around the neurons, mild demyelinated and vacuolar degeneration in both group B and C at C_6/7 level 24 h after injury. Pathological changes deteriorated at 48 h after injury. Conclusion Percutaneous epidural balloon catheter insertion can avoid surgical exposure of normal tissues around the spinal cord, and it may serve as a method for establishing acute cervical spinal cord injury model simulating the clinical condition.