Acupuncture has demonstrated its efficacy as a treatment for Parkinson's disease (PD). Thus, the objective of this study was to investigate the potential mechanisms underlying acupuncture's effects on PD treatment. Our approach involved several steps. Firstly, we assessed the behavioral changes in PD rats, the modulation of dopamine (DA) and 5-hydroxytryptamine (5 -HT) levels in the striatum, as well as the alteration in alpha-synuclein (alpha-syn) levels in the midbrain, aiming to evaluate the efficacy of acupuncture in PD treatment. Secondly, we selected endoplasmic reticulum (ER) stress inhibitors and activators to assess the impact of ER stress on PD rats. Lastly, we utilized an IRE1 inhibitor to observe the influence of acupuncture on the IRE1/XBP1 pathway in PD rats. The findings of this study revealed that acupuncture improved the autonomous motor function, balance ability, coordination, and sensory motor integration function in the PD model rats. Additionally, it increased the levels of DA and 5 -HT in the striatum while decreasing the levels of alpha-syn in the midbrain. Acupuncture also activated the expression of ER stress in the midbrain and upregulated the expression of IRE1/XBP1 in the striatum of PD model rats. Based on these results, we concluded that acupuncture may enhance the behavior of PD rats by activating the IRE1/XBP1 ER stress pathway, associated with the reduction of midbrain alpha-syn expression and the increase in striatal DA and 5 -HT levels in unilateral 6-OHDA lesioned rats.