Recently, sentinel lymph nodes (LNs) have been recognized as a starting point of hematogenous metastasis; thus, an increase in the control rate of LN metastasis is expected to improve the survival rate. Although surgical treatment and radiation therapy are commonly used for the radical treatment of LNs, these treatments are associated with lymphedema, pain, and an extended hospital stay. In a recent mouse study, activation of metastatic tumors in distant organs was reported after removing LNs, with or without metastasis to the LNs. Thus, there is the necessity for cancer treatment that can replace LN removal. Here, we evaluated the treatment efficacy of lymphatic drug delivery system (LDDS) with osmotic pressure and viscosity escalated Docetaxel at the early stage of LN metastasis. MXH10/Mo/lpr mice were inoculated with mouse breast cancer cells into Subiliac LN to create the metastatic mouse model. Docetaxel was injected into mouse mammary carcinoma cells inoculated LN as a single shot (SS) or double shot (DS) to understand the therapeutic mechanism of a single shot or double shot intervention using an in vivo imaging system, histology, and qPCR. The results showed that the DS administration of docetaxel at 1,960 kPa (12 mPa∙s) had better therapeutic outcomes with increased complete response and improved survival with reduced adverse events. The results also revealed that administration of a DS of docetaxel enhances differentiation of T helper cells, and improves survival and therapeutic outcomes. From a safety perspective, LDDS-administered DS of low-concentration docetaxel without any other anticancer treatments to LNs a novel approach to cancer management of LN metastasis. We emphasize that LDDS is a groundbreaking method of delivering anticancer drugs specifically to cancer susceptible LNs and is designed to enhance the effectiveness of cancer treatment while minimizing side effects.