The second-most frequent neurodegenerative condition worldwide is Parkinson's disease. The goal of this study was to examine the effects of DMSO in a rat model of Parkinson's disease caused by rotenone. Due to its capacity to increase the penetration of potential water-insoluble drugs into the central nervous system, DMSO has been widely used in preclinical and clinical studies. In this study, we examined how three weeks of rotenone and DMSO treatment affected hippocampal neuronal activity and neuronal response properties in rats. The toxic effects of rotenone on DMSO-treated hippocampal CA1 and CA3 cells were compared. We found that rotenone caused profound morphological changes in the hippocampal cells. We showed that pyramidal cells and Nissl bodies in the hippocampus CA1 and CA3 areas of rats given rotenone therapy dramatically improved after DMSO treatment. DMSO effectively suppressed both inward and outward currents. Background and evoked spike activities were recorded in the hippocampus of rats administered DMSO (1 ml/kg i.p. for 3 weeks). Rotenone enhances TP and induces a milder TD effect, while DMSO also enhances TP but induces a stronger TD effect. The analysis revealed inhibitory effects in the hippocampus in response to high-frequency stimulation (HFS; 100 Hz for 1 s) of the ipsilateral entorhinal cortex.