Objective To investigate the influences of propofol on cognitive impairment, nuclear factor E2-related factor 2 (Nrf2) pathway and receptor for advanced glycation end product/nuclear factor-κB (RAGE/NF-κB) signaling pathway in rats with Parkinson′s disease (PD).Methods PD rat model was established by intraperitoneal injection of MPTP. The rats were divided into control group (Control group), model group (PD group), low and high dose propofol treatment groups (Propofol-L group, Propofol-H group, 25 and 50 mg/kg propofol intraperitoneal injection), according to the method of random number table. Morris water maze test and Y-maze test were performed to detect cognitive function in rats. HE staining was used to observe the pathological changes in the substantia nigra. The levels of oxidative stress factors and inflammatory factors and the protein expressions of tyrosine hydroxylase (TH), RAGE, p-NF-κB p65, Nrf2 and HO-1 in the substantia nigra were detected. Results Compared with the control group, the escape latency of the PD group increased, the percentage of residence time in the target quadrant, the number of crossing the target quadrant, and the rate of spontaneous alternation were significantly reduced (P<0.05), the pathological changes occurred in brain tissue, the MDA activity, the levels of TNF-α and IL-1β, and the protein expressions of RAGE, p-NF-κB p65 in the substantia nigra were significantly increased, and the activities CAT of SOD and the protein expressions of TH, Nrf2 and HO-1 were significantly decreased (P<0.05). Compared with PD group, the escape latency of rats in Propofo-L and Propofo-H groups was decreased, the percentage of retention time in the target quadrant, the number of crossing the target quadrant and the spontaneous alternations rate were increased significantly (P<0.05), and the lesions of brain tissue were reduced. MDA activity, TNF-α and IL-1β levels, RAGE and P-NF-κB p65 protein expression were significantly decreased in the substantia nigra, while CAT and SOD activities and TH, Nrf2 and HO-1 protein expressions were significantly increased in a dose-dependent manner (P<0.05).Conclusion Propofol can improve cognitive impairment in PD rats, and its mechanism may be related to the activation of Nrf2 signaling pathway and the inhibition of RAGE/NF-κB signaling pathway