Objective: To observe the effects of activation or blockade of the prelimbic (PrL) α1-adrenoceptors on anxiety-like behaviors and amygdaloid neural activities in rats with Parkinson's disease (PD). Methods: The rat model of PD was established by 6-hydroxydopamine (6-OHDA) unilateral lesion of the medial forebrain bundle (MFB). Then the anxiety-like behavior of rats was detected by the open field test. In addition, the changes of anxiety-like behavior, the effects of PrL α1-adrenoceptor stimulation on monoamines and c-Fos expression in the amygdala were also observed after local injection of the selective α1-adrenoceptor agonist or antagonist into the PrL by guided cannula. Results: Unilateral 6-OHDA lesions of the MFB in rats induced anxiety-like behaviors (P<0.001). Furthermore, activation of the PrL α1-adrenoceptors significantly induced or enhanced anxiety-like behaviors in the rats (sham group: P<0.001; lesion group: P<0.05), while blockade of the α1-adrenoceptors produced anxiolytic effects (sham group: P<0.001; lesion group: P<0.05). Then activation of the PrL α1-adrenoceptors increased the levels of DA and 5-HT while blockade of the PrL α1-adrenoceptors decreased DA and 5-HT levels in the amygdala in sham-operated rats (DA & 5-HT: P<0.001). However, compared to those of sham-operated rats, activation of the PrL α1-adrenoceptors increased the levels of NA and 5-HT while blockade of the PrL α1-adrenoceptors decreased NA and 5-HT levels in the amygdala in the lesioned rats (NA & 5-HT: P<0.001). In addition, the density of c-Fos immunoreactive positive neurons in the amygdala increased after intra-PrL injection α1-adrenoceptors agonist phenylephrine (sham group & lesion group: P<0.001). Conclusion: These findings indicate that changed neural activities in the amygdala after activation or blockade of the PrL α1-adrenoceptors are involved in regulating anxiety-like behaviors in PD rats.