Objective To establish an appropriate animal model of brain metastases from lung cancer in nude mice by thoracic orthotopic implantation in the chest or left ventricular injection, and to serve further studies on the mechanisms of lung cancer brain metastasis. Methods PC-9 cells (1×10⁶/0.1 mL) in logarithmic phase were respectively injected into 18 nude mice by orthotopic implantation in the chest or left ventricular injection (n=9 each group). The statuses of nude mice were observed after implantation. Animals showing clear signs of dyscrasia were killed. At autopsy, the lung, brain, liver and kidney were removed and histological sections were stained with H/E to detect the presence of tumor cells. Results In the thoracic orthotopic implantation group, three weeks after implantation, the number 4, 6, 9 mice showed tumor nodules in the chest wall, they began to lose weight in the fourth to sixth week differently, showing signs of dyscrasia gradually, and were sacrificed at the fifth to seventh week. The thoracotomy revealed that the whole thorax was occupied by many large lung cancer masses, spreading into bilateral ribs, pleura and spinal vertebra, with scarce eroded, compressed, pale and distorted lung tissues left. Histological examination with HE staining showed the presence of neoplasms in their lung tissues but only the number 6 mouse showed metastatic lesions in the brain tissue. In the left ventricular injection group, the mice almost began to lose weight in the third week simultaneously and became moribund slowly, which were all sacrificed at the fourth week. After thoracotomy, the thoraxes were clear except the number 11 and 18 mice which appeared 2-3 tiny tumor foci in the chest wall, with normal lung tissues. Histological examination with HE staining showed the presence of brain metastases in all the nine mice. The rate of brain metastases from lung cancer in the left ventricular injection group was 100%, compared with 11.1% in the thoracic orthotopic implantation group. Conclusions The establishment method of mouse model by left ventricular injection shows significantly higher rate of lung cancer brain metastases than that by thoracic orthotopic implantation.