Background: Paclitaxel is a taxane-based chemotherapeutic agent used as a treatment in breast cancer. There is no effective prevention or treatment strategy for the most common side effect of peripheral neuropathy. In this manuscript, we reviewed the molecular mechanisms that contribute to paclitaxel-induced peripheral neuropathy (PIPN) with an emphasis on immune-related processes. Methods: A systematic search of the literature was conducted in PubMed, EMBASE and Cochrane Library. The SYRCLE's risk of bias tool was used to assess internal validity. Results: 156 studies conducted with rodent models were included. The risk of bias was high due to unclear methodology. Paclitaxel induces changes in myelinated axons, mitochondrial dysfunction, and mechanical hypersensitivity by affecting ion channels expression and function and facilitating spinal transmission. Paclitaxel-induced inflammatory responses are important contributors to PIPN. Conclusion: Immune-related processes are an important mechanism contributing to PIPN. Studies in humans that validate these mechanistic data are highly needed to facilitate the development of therapeutic strategies.