Abstract: In order to decrease the metabolic rate and to extend the action of nicotine, and to explore the intervention effect and mechanism of sustained nicotine release on Parkinson's diseased mice (PD mice), a nano hydrogel for loading nicotine (Nic@NHG) was established using a phase transition microemulsion method, and the nicotine loading ratio and sustained release efficiency using the animal model were studied. Animal behavior analysis was conducted to evaluate the improvement effect of sustained nicotine release on PD mice. Molecular biology methods were employed to analyze the expression levels and phosphorylation status of key proteins in signal pathways to elucidate the molecular mechanism of intervention from Nic@NHG's in Parkinson's disease (PD). The results showed that: 1) Sodium alginate nano hydrogel could effectively load and sustainably released nicotine, and the loading rate exceeded 90% for nicotine with mass concentrations of 1.0, 1.5 and 2.0 mg/mL. The effective duration of sustained release of nicotine at different mass concentrations in Nic@NHG exceeded 6 hours, and the blood metabolic duration was nearly 12 hours, approximately twice of that in the nicotine system. 2) Nic@NHG effectively alleviated the anxiety and improved muscle symptoms of the PD mice, with all major indicators showing significant improvement compared to the nicotine system, and the intervention effect was dose dependent. The intervention effect at 2.0 mg/mL was significantly better than that at 1.0 mg/mL, and the intervention effects at the loading concentrations of 2.0 and 3.0 mg/mL were similar. 3) Nic@NHG effectively inhibited inflammatory reactions and neuronal apoptosis in PD mice, demonstrating a significantly better inhibitory effect than the nicotine system. 4) Nic@NHG effectively inhibited abnormal phosphorylation in PI3K/Akt and JAK2/STAT3 signal pathways of PD mice, upregulated Survivin, downregulated Caspase-3 and proinflammatory factors such as IL-6, TNF-α, iNOS, and MCP-1, and the effects were significantly better than those of the nicotine system, which was close to the experimental results of normal mice. Compared to nicotine, Nic@NHG further inhibited the abnormal phosphorylation in PI3K/Akt and JAK2/STAT3 signal pathways, regulated the expression levels of key proteins, thereby alleviated the anxiety and improved muscle symptoms in PD mice.