The purpose of the study was to evaluate the potential of lymphatic chemotherapy in inducing apoptosis in axillary lymph node metastases in a rabbit breast cancer model. A total of 30 female New Zealand rabbits with mammary implantation of VX2 carcinomas were divided into three groups randomly, with ten in each. Treatment was carried out once axillary lymph node reached 5 mm in the maximum diameter. Group A received a subcutaneous injection of liposomal adriamycin (LADR) adjacent to the breast tumor. Group B received free adriamycin (FADR) administered into the auricular vein. Group C received a sham treatment. The dose of adriamycin in each administration was 1 mg/kg in groups A and B. Treatment was repeated every 48 h. Axillary lymph nodes were dissected out 48 h after the third treatment. The nodal sizes before and after the treatment were measured. The therapeutic effect was evaluated in terms of the node volume ratio and apoptotic index (AI) of metastatic cells in nodes identified with TUNEL technique. The significance of difference was determined with one-way ANOVA followed by the Fischer LSD test. Compared to group C, the enlargement of lymph nodes was sufficiently slowed down in both groups A and B, and group A showed a further strong inhibitory effect than group B (P = 0.002). Apparent VX2 cell apoptosis was detected in the lymph nodes of groups A and B. The average AI in group B (15.31%) was significantly higher than in group C (5.16%). The highest AI was found in animals of group A (21.73%), with a further significant difference from group B (P = 0.000). These data suggest that lymphatic chemotherapy appears to be a promising method to induce apoptosis in lymph node metastases