Dissolving microneedles (DMNs) are widely used in drug delivery systems since they are based on one-step application, which is simple and convenient for patients, especially for the patients such as diabetes who need daily or long-term self-administration. In general, the matrix materials of DMNs are water-soluble materials that can release the encapsulated drugs gradually by dissolving in the skin without generating sharp needle waste. However, the matrix materials of DMNs will also leave in the skin after application. Thus, it is vital to evaluate whether the matrix material of DMNs dissolved in the skin will cause health risks such as toxicity to the body or some skin-related complications to patients who frequent or long-term administration. In this work, PVA, as one of the typical matrix materials of DMNs, was selected to prepare the DMNs to research the safety of PVA-based MNs to the body after being dissolved in the skin. Briefly, in a 160 - days trial, the healthy mice were daily administrated by PVA MNs. The results showed that PVA materials mainly accumulated in the skin tissues of mice after dissolving and the concentration of PVA in the insertion sites gradually decreased and was almost undetectable at 6 days after administration. The observation of general conditions, blood hematological analysis and histological examinations of the mice demonstrated that the PVA-based MNs do not cause appreciable toxicity to the healthy mice after daily insertion in a 160 - days trial. Altogether, these results encourage further studies of PVA MNs for biomedical applications and support translation of PVA-based DMNs from pre-clinical development into clinical trials.