Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) with subsequent motor manifestations. This study aimed to assess the ameliorative effects of nicotine, in rotenone-induced PD rat model. Thirty adult male Albino Wistar rats were divided into three equal groups. Group I received an injection of normal saline. Group II received subcutaneous injection of rotenone at a dose of 1.5 mg/kg every other day. Group III received rotenone in the same previous dose and nicotine at a dose of 1.5 mg/kg daily. After 11 days of treatment, body weight (BW) and rat motor behavior were estimated. Specimens from the midbrain were processed for light and electron microscopy. The expression of tyrosine hydroxylase (TH), α-synuclein, and GFAP was examined. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), and striatal levels of dopamine (DA) were analyzed. Group III revealed a significant improvement in BW and motor activity. Nicotine upregulated the expression of TH, downregulated the expression of α-synuclein and GFAP. The levels of MDA and TAC were improved but were still far from those of the control. Striatal DA levels increased. Nicotine activated the neurons and glial cells. The vascular endothelium, however, did not elicit improvement. Although nicotine ameliorated the loss of the dopaminergic neurons and motor deficit, it did not show improvement of vascular endothelium. It is still necessary to examine nicotin’s ability to maintain the dopaminergic neurons in a good functioning state.